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Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease

Published online by Cambridge University Press:  23 December 2009

J. BRIAN de SOUZA
Affiliation:
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Department of Immunology and Molecular Pathology, University College London Medical School, 46 Cleveland Street, London W1T 4JF, UK
JULIUS C. R. HAFALLA
Affiliation:
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
ELEANOR M. RILEY
Affiliation:
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
KEVIN N. COUPER*
Affiliation:
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
*
*Corresponding author: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Tel: +44 207 927 2690. Fax: +44 207 927 2807. E-mail: [email protected]

Summary

Cerebral malaria is a life-threatening complication of malaria infection. The pathogenesis of cerebral malaria is poorly defined and progress in understanding the condition is severely hampered by the inability to study in detail, ante-mortem, the parasitological and immunological events within the brain that lead to the onset of clinical symptoms. Experimental murine models have been used to investigate the sequence of events that lead to cerebral malaria, but there is significant debate on the merits of these models and whether their study is relevant to human disease. Here we review the current understanding of the parasitological and immunological events leading to human and experimental cerebral malaria, and explain why we believe that studies with experimental models of CM are crucial to define the pathogenesis of the condition.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Adams, S., Turner, G. D., Nash, G. B., Micklem, K., Newbold, C. I. and Craig, A. G. (2000). Differential binding of clonal variants of Plasmodium falciparum to allelic forms of intracellular adhesion molecule 1 determined by flow adhesion assay. Infection and Immunity 68, 264269.CrossRefGoogle ScholarPubMed
Aikawa, M., Brown, A., Smith, C. D., Tegoshi, T., Howard, R. J., Hasler, T. H., Ito, Y., Perry, G., Collins, W. E. and Webster, K. (1992). A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus monkeys. American Journal of Tropical Medicine and Hygiene 46, 391397.CrossRefGoogle ScholarPubMed
Amani, V., Vigario, A. M., Belnoue, E., Marussig, M., Fonseca, L., Mazier, D. and Renia, L. (2000). Involvement of IFN-gamma receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection. European Journal of Immunology 30, 16461655.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Amante, F. H., Stanley, A. C., Randall, L. M., Zhou, Y., Haque, A., Mcsweeney, K., Waters, A. P., Janse, C. J., Good, M. F., Hill, G. R. and Engwerda, C. R. (2007). A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. American Journal of Pathology 171, 548559.Google Scholar
Artavanis-Tsakonas, K., Tongren, J. E. and Riley, E. M. (2003). The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology. Clinical and Experimental Immunology 133, 145152.Google Scholar
Bagot, S., Campino, S., Penha-Goncalves, C., Pied, S., Cazenave, P. A. and Holmberg, D. (2002). Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain. Proceedings of the National Academy of Sciences, USA 99, 99199923.Google Scholar
Baruch, D. I., Ma, X. C., Singh, H. B., Bi, X., Pasloske, B. L. and Howard, R. J. (1997). Identification of a region of PfEMP1 that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence. Blood 90, 37663775.Google Scholar
Baruch, D. I., Pasloske, B. L., Singh, H. B., Bi, X., Ma, X. C., Feldman, M., Taraschi, T. F. and Howard, R. J. (1995). Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82, 7787.Google Scholar
Bate, C. A. and Kwiatkowski, D. P. (1994). Stimulators of tumour necrosis factor production released by damaged erythrocytes. Immunology 83, 256261.Google ScholarPubMed
Beare, N. A., Taylor, T. E., Harding, S. P., Lewallen, S. and Molyneux, M. E. (2006). Malarial retinopathy: a newly established diagnostic sign in severe malaria. American Journal of Tropical Medicine and Hygiene 75, 790797.CrossRefGoogle ScholarPubMed
Beeson, J. G., Reeder, J. C., Rogerson, S. J. and Brown, G. V. (2001). Parasite adhesion and immune evasion in placental malaria. Trends in Parasitology 17, 331337.CrossRefGoogle ScholarPubMed
Beghdadi, W., Porcherie, A., Schneider, B. S., Dubayle, D., Peronet, R., Huerre, M., Watanabe, T., Ohtsu, H., Louis, J. and Mecheri, S. (2008). Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease. Journal of Experimental Medicine 205, 395408.Google Scholar
Bellamy, R., Kwiatkowski, D. and Hill, A. V. (1998). Absence of an association between intercellular adhesion molecule 1, complement receptor 1 and interleukin 1 receptor antagonist gene polymorphisms and severe malaria in a West African population. Transactions of the Royal Society of Tropical Medicine and Hygiene 92, 312316.Google Scholar
Belnoue, E., Kayibanda, M., Vigario, A. M., Deschemin, J. C., Van Rooijen, N., Viguier, M., Snounou, G. and Renia, L. (2002). On the pathogenic role of brain-sequestered alphabeta CD8+ T cells in experimental cerebral malaria. Journal of Immunology 169, 63696375.CrossRefGoogle ScholarPubMed
Belnoue, E., Potter, S. M., Rosa, D. S., Mauduit, M., Gruner, A. C., Kayibanda, M., Mitchell, A. J., Hunt, N. H. and Renia, L. (2008). Control of pathogenic CD8+ T cell migration to the brain by IFN-gamma during experimental cerebral malaria. Parasite Immunology 30, 544553.Google Scholar
Berendt, A. R., Tumer, G. D. and Newbold, C. I. (1994). Cerebral malaria: the sequestration hypothesis. Parasitology Today 10, 412414.Google Scholar
Boivin, M. J., Bangirana, P., Byarugaba, J., Opoka, R. O., Idro, R., Jurek, A. M. and John, C. C. (2007). Cognitive impairment after cerebral malaria in children: a prospective study. Pediatrics 119, e360366.CrossRefGoogle ScholarPubMed
Buffet, P. A., Gamain, B., Scheidig, C., Baruch, D., Smith, J. D., Hernandez-Rivas, R., Pouvelle, B., Oishi, S., Fujii, N., Fusai, T., Parzy, D., Miller, L. H., Gysin, J. and Scherf, A. (1999). Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection. Proceedings of the National Academy of Sciences, USA 96, 1274312748.CrossRefGoogle ScholarPubMed
Cabantous, S., Doumbo, O., Ranque, S., Poudiougou, B., Traore, A., Hou, X., Keita, M. M., Cisse, M. B., Dessein, A. J. and Marquet, S. (2006). Alleles 308A and 238A in the tumor necrosis factor alpha gene promoter do not increase the risk of severe malaria in children with Plasmodium falciparum infection in Mali. Infection and Immunity 74, 70407042.Google Scholar
Campanella, G. S., Tager, A. M., El Khoury, J. K., Thomas, S. Y., Abrazinski, T. A., Manice, L. A., Colvin, R. A. and Luster, A. D. (2008). Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proceedings of the National Academy of Sciences, USA 105, 48144819.Google Scholar
Campino, S., Bagot, S., Bergman, M. L., Almeida, P., Sepulveda, N., Pied, S., Penha-Goncalves, C., Holmberg, D. and Cazenave, P. A. (2005). Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity. Genes & Immunity 6, 416421.Google Scholar
Carlton, J. M., Angiuoli, S. V., Suh, B. B., Kooij, T. W., Pertea, M., Silva, J. C., Ermolaeva, M. D., Allen, J. E., Selengut, J. D., Koo, H. L., Peterson, J. D., Pop, M., Kosack, D. S., Shumway, M. F., Bidwell, S. L., Shallom, S. J., Van Aken, S. E., Riedmuller, S. B., Feldblyum, T. V., Cho, J. K., Quackenbush, J., Sedegah, M., Shoaibi, A., Cummings, L. M., Florens, L., Yates, J. R., Raine, J. D., Sinden, R. E., Harris, M. A., Cunningham, D. A., Preiser, P. R., Bergman, L. W., Vaidya, A. B., Van Lin, L. H., Janse, C. J., Waters, A. P., Smith, H. O., White, O. R., Salzberg, S. L., Venter, J. C., Fraser, C. M., Hoffman, S. L., Gardner, M. J. and Carucci, D. J. (2002). Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature, London 419, 512519.CrossRefGoogle ScholarPubMed
Carter, J. A., Mung'ala-Odera, V., Neville, B. G., Murira, G., Mturi, N., Musumba, C. and Newton, C. R. (2005 a). Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. Journal of Neurology, Neurosurgery & Psychiatry 76, 476481.Google Scholar
Carter, J. A., Ross, A. J., Neville, B. G., Obiero, E., Katana, K., Mung'ala-Odera, V., Lees, J. A. and Newton, C. R. (2005 b). Developmental impairments following severe falciparum malaria in children. Tropical Medicine & International Health 10, 310.Google Scholar
Casals-Pascual, C., Idro, R., Gicheru, N., Gwer, S., Kitsao, B., Gitau, E., Mwakesi, R., Roberts, D. J. and Newton, C. R. (2008). High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria. Proceedings of the National Academy of Sciences, USA 105, 26342639.Google Scholar
Casals-Pascual, C., Idro, R., Picot, S., Roberts, D. J. and Newton, C. R. (2009). Can erythropoietin be used to prevent brain damage in cerebral malaria? Trends in Parasitology 25, 3036.Google Scholar
Chakravorty, S. J. and Craig, A. (2005). The role of ICAM-1 in Plasmodium falciparum cytoadherence. European Journal of Cell Biology 84, 1527.Google Scholar
Chakravorty, S. J., Hughes, K. R. and Craig, A. G. (2008). Host response to cytoadherence in Plasmodium falciparum. Biochemical Society Transactions 36, 221228.Google Scholar
Chang-Ling, T., Neill, A. L. and Hunt, N. H. (1992). Early microvascular changes in murine cerebral malaria detected in retinal wholemounts. American Journal of Pathology 140, 11211130.Google ScholarPubMed
Chen, Q., Barragan, A., Fernandez, V., Sundstrom, A., Schlichtherle, M., Sahlen, A., Carlson, J., Datta, S. and Wahlgren, M. (1998). Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum. Journal of Experimental Medicine 187, 1523.Google Scholar
Clark, C. J., Phillips, R. S., McMillan, R. B., Montgomery, I. O. and Stone, T. W. (2005). Differences in the neurochemical characteristics of the cortex and striatum of mice with cerebral malaria. Parasitology 130, 2329.Google Scholar
Clark, I. A., Awburn, M. M., Whitten, R. O., Harper, C. G., Liomba, N. G., Molyneux, M. E. and Taylor, T. E. (2003). Tissue distribution of migration inhibitory factor and inducible nitric oxide synthase in falciparum malaria and sepsis in African children. Malaria Journal 2, 6.CrossRefGoogle ScholarPubMed
Clark, I. A., Budd, A. C., Alleva, L. M. and Cowden, W. B. (2006). Human malarial disease: a consequence of inflammatory cytokine release. Malaria Journal 5, 85.Google Scholar
Clark, T. G., Diakite, M., Auburn, S., Campino, S., Fry, A. E., Green, A., Richardson, A., Small, K., Teo, Y. Y., Wilson, J., Jallow, M., Sisay-Joof, F., Pinder, M., Griffiths, M. J., Peshu, N., Williams, T. N., Marsh, K., Molyneux, M. E., Taylor, T. E., Rockett, K. A. and Kwiatkowski, D. P. (2009). Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations. Journal of Infectious Diseases 199, 569575.CrossRefGoogle ScholarPubMed
Coltel, N., Combes, V., Wassmer, S. C., Chimini, G. and Grau, G. E. (2006). Cell vesiculation and immunopathology: implications in cerebral malaria. Microbes and Infection 8, 23052316.Google Scholar
Combes, V., Rosenkranz, A. R., Redard, M., Pizzolato, G., Lepidi, H., Vestweber, D., Mayadas, T. N. and Grau, G. E. (2004). Pathogenic role of P-selectin in experimental cerebral malaria: importance of the endothelial compartment. American Journal of Pathology 164, 781786.Google Scholar
Couper, K. N., Blount, D. G., Hafalla, J. C., Van Rooijen, N., De Souza, J. B. and Riley, E. M. (2007). Macrophage-mediated but gamma interferon-independent innate immune responses control the primary wave of Plasmodium yoelii parasitemia. Infection and Immunity 75, 58065818.CrossRefGoogle ScholarPubMed
Couper, K. N., Blount, D. G., Wilson, M. S., Hafalla, J. C., Belkaid, Y., Kamanaka, M., Flavell, R. A., De Souza, J. B. and Riley, E. M. (2008). IL-10 from CD4CD25Foxp3CD127 adaptive regulatory T cells modulates parasite clearance and pathology during malaria infection. PLoS Pathogens 4, e1000004.CrossRefGoogle ScholarPubMed
Crawley, J., Smith, S., Kirkham, F., Muthinji, P., Waruiru, C. and Marsh, K. (1996). Seizures and status epilepticus in childhood cerebral malaria. Quarterly Journal of Medicine 89, 591597.Google Scholar
Cunningham, D. A., Jarra, W., Koernig, S., Fonager, J., Fernandez-Reyes, D., Blythe, J. E., Waller, C., Preiser, P. R. and Langhorne, J. (2005). Host immunity modulates transcriptional changes in a multigene family (yir) of rodent malaria. Molecular Microbiology 58, 636647.Google Scholar
Curfs, J. H., Hermsen, C. C., Kremsner, P., Neifer, S., Meuwissen, J. H., Van Rooyen, N. and Eling, W. M. (1993 b). Tumour necrosis factor-alpha and macrophages in Plasmodium berghei-induced cerebral malaria. Parasitology 107, 125134.CrossRefGoogle ScholarPubMed
Curfs, J. H., Van Der Meide, P. H., Billiau, A., Meuwissen, J. H. and Eling, W. M. (1993 a). Plasmodium berghei: recombinant interferon-gamma and the development of parasitemia and cerebral lesions in malaria-infected mice. Experimental Parasitology 77, 212223.Google Scholar
De Souza, J. B. and Riley, E. M. (2002). Cerebral malaria: the contribution of studies in animal models to our understanding of immunopathogenesis. Microbes and Infection 4, 291300.CrossRefGoogle ScholarPubMed
Del Portillo, H. A., Fernandez-Becerra, C., Bowman, S., Oliver, K., Preuss, M., Sanchez, C. P., Schneider, N. K., Villalobos, J. M., Rajandream, M. A., Harris, D., Pereira Da Silva, L. H., Barrell, B. and Lanzer, M. (2001). A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature, London 410, 839842.Google Scholar
Delahaye, N. F., Coltel, N., Puthier, D., Barbier, M., Benech, P., Joly, F., Iraqi, F. A., Grau, G. E., Nguyen, C. and Rihet, P. (2007). Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice. BMC Genomics, 8, 452467.Google Scholar
Desruisseaux, M. S., Gulinello, M., Smith, D. N., Lee, S. C., Tsuji, M., Weiss, L. M., Spray, D. C. and Tanowitz, H. B. (2008). Cognitive dysfunction in mice infected with Plasmodium berghei strain ANKA. Journal of Infectious Diseases 197, 16211627.Google Scholar
Dewalick, S., Amante, F. H., Mcsweeney, K. A., Randall, L. M., Stanley, A. C., Haque, A., Kuns, R. D., Macdonald, K. P., Hill, G. R. and Engwerda, C. R. (2007). Cutting edge: conventional dendritic cells are the critical APC required for the induction of experimental cerebral malaria. Journal of Immunology 178, 60336037.CrossRefGoogle ScholarPubMed
Dondorp, A., Nosten, F., Stepniewska, K., Day, N. and White, N. (2005 a). Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366, 717725.Google Scholar
Dondorp, A. M., Desakorn, V., Pongtavornpinyo, W., Sahassananda, D., Silamut, K., Chotivanich, K., Newton, P. N., Pitisuttithum, P., Smithyman, A. M., White, N. J. and Day, N. P. (2005 b). Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Medicine 2, e204.CrossRefGoogle ScholarPubMed
Elhassan, I. M., Hviid, L., Satti, G., Akerstrom, B., Jakobsen, P. H., Jensen, J. B. and Theander, T. G. (1994). Evidence of endothelial inflammation, T cell activation, and T cell reallocation in uncomplicated Plasmodium falciparum malaria. American Journal of Tropical Medicine and Hygiene 51, 372379.Google Scholar
Engwerda, C. R., Beattie, L. and Amante, F. H. (2005). The importance of the spleen in malaria. Trends in Parasitology 21, 7580.CrossRefGoogle ScholarPubMed
Engwerda, C. R., Mynott, T. L., Sawhney, S., De Souza, J. B., Bickle, Q. D. and Kaye, P. M. (2002). Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria. Journal of Experimental Medicine 195, 13711377.Google Scholar
Esslinger, C. W., Picot, S. and Ambroise-Thomas, P. (1994). Intra-erythrocytic Plasmodium falciparum induces up-regulation of inter-cellular adhesion molecule-1 on human endothelial cells in vitro. Scandinavian Journal of Immunology 39, 229232.Google Scholar
Faille, D., Combes, V., Mitchell, A. J., Fontaine, A., Juhan-Vague, I., Alessi, M. C., Chimini, G., Fusai, T. and Grau, G. E. (2009). Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium. FASEB Journal 23, 34493458.CrossRefGoogle ScholarPubMed
Favre, N., Da Laperousaz, C., Ryffel, B., Weiss, N. A., Imhof, B. A., Rudin, W., Lucas, R. and Piguet, P. F. (1999). Role of ICAM-1 (CD54) in the development of murine cerebral malaria. Microbes and Infection 1, 961968.Google Scholar
Fernandez-Reyes, D., Craig, A. G., Kyes, S. A., Peshu, N., Snow, R. W., Berendt, A. R., Marsh, K. and Newbold, C. I. (1997). A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Human Molecular Genetics 6, 13571360.Google Scholar
Finley, R., Weintraub, J., Louis, J. A., Engers, H. D., Zubler, R. and Lambert, P. H. (1983). Prevention of cerebral malaria by adoptive transfer of malaria-specific cultured T cells into mice infected with Plasmodium berghei. Journal of Immunology 131, 15221526.CrossRefGoogle ScholarPubMed
Franke-Fayard, B., Janse, C. J., Cunha-Rodrigues, M., Ramesar, J., Buscher, P., Que, I., Lowik, C., Voshol, P. J., Den Boer, M. A., Van Duinen, S. G., Febbraio, M., Mota, M. M. and Waters, A. P. (2005). Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proceedings of the National Academy of Sciences, USA 102, 1146811473.CrossRefGoogle ScholarPubMed
Fried, M. and Duffy, P. E. (2002). Two DBLgamma subtypes are commonly expressed by placental isolates of Plasmodium falciparum. Molecular and Biochemical Parasitology 122, 201210.Google Scholar
Fry, A. E., Auburn, S., Diakite, M., Green, A., Richardson, A., Wilson, J., Jallow, M., Sisay-Joof, F., Pinder, M., Griffiths, M. J., Peshu, N., Williams, T. N., Marsh, K., Molyneux, M. E., Taylor, T. E., Rockett, K. A. and Kwiatkowski, D. P. (2008). Variation in the ICAM1 gene is not associated with severe malaria phenotypes. Genes & Immunity 9, 462469.Google Scholar
Gamain, B., Smith, J. D., Avril, M., Baruch, D. I., Scherf, A., Gysin, J. and Miller, L. H. (2004). Identification of a 67-amino-acid region of the Plasmodium falciparum variant surface antigen that binds chondroitin sulphate A and elicits antibodies reactive with the surface of placental isolates. Molecular Microbiology 53, 445455.CrossRefGoogle ScholarPubMed
Gardner, J. P., Pinches, R. A., Roberts, D. J. and Newbold, C. I. (1996). Variant antigens and endothelial receptor adhesion in Plasmodium falciparum. Proceedings of the National Academy of Sciences, USA 93, 35033508.CrossRefGoogle ScholarPubMed
Good, M. F., Xu, H., Wykes, M. and Engwerda, C. R. (2005). Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine research. Annual Review of Immunology 23, 6999.Google Scholar
Gramaglia, I., Sobolewski, P., Meays, D., Contreras, R., Nolan, J. P., Frangos, J. A., Intaglietta, M. and Van Der Heyde, H. C. (2006). Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nature Medicine 12, 14171422.Google Scholar
Grau, G. E., Fajardo, L. F., Piguet, P. F., Allet, B., Lambert, P. H. and Vassalli, P. (1987). Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237, 12101212.Google Scholar
Grau, G. E., Heremans, H., Piguet, P. F., Pointaire, P., Lambert, P. H., Billiau, A. and Vassalli, P. (1989). Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. Proceedings of the National Academy of Sciences, USA 86, 55725574.CrossRefGoogle ScholarPubMed
Gray, C., McCormick, C., Turner, G. and Craig, A. (2003). ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow. Molecular and Biochemical Parasitology 128, 187193.Google Scholar
Gysin, J., Aikawa, M., Tourneur, N. and Tegoshi, T. (1992). Experimental Plasmodium falciparum cerebral malaria in the squirrel monkey Saimiri sciureus. Experimental Parasitology 75, 390398.Google Scholar
Haldar, K., Murphy, S. C., Milner, D. A. and Taylor, T. E. (2007). Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annual Review of Pathology 2, 217249.CrossRefGoogle ScholarPubMed
Hansen, D. S., Bernard, N. J., Nie, C. Q. and Schofield, L. (2007). NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium berghei-mediated cerebral malaria. Journal of Immunology 178, 57795788.CrossRefGoogle Scholar
Hau, J. and Van Hoosier, G. L. Jr. (2005). Handbook of Laboratory Animal Science. 2nd Edn. CRC Press, Boca Raton, FL, USA.Google Scholar
Hearn, J., Rayment, N., Landon, D. N., Katz, D. R. and De Souza, J. B. (2000). Immunopathology of cerebral malaria: morphological evidence of parasite sequestration in murine brain microvasculature. Infection and Immunity 68, 53645376.CrossRefGoogle ScholarPubMed
Heddini, A., Pettersson, F., Kai, O., Shafi, J., Obiero, J., Chen, Q., Barragan, A., Wahlgren, M. and Marsh, K. (2001). Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors. Infection and Immunity 69, 58495856.Google Scholar
Hermsen, C., Van De Wiel, T., Mommers, E., Sauerwein, R. and Eling, W. (1997). Depletion of CD4+ or CD8+ T-cells prevents Plasmodium berghei induced cerebral malaria in end-stage disease. Parasitology 114, 712.Google Scholar
Ho, M., Schollaardt, T., Niu, X., Looareesuwan, S., Patel, K. D. and Kubes, P. (1998). Characterization of Plasmodium falciparum-infected erythrocyte and P-selectin interaction under flow conditions. Blood 91, 48034809.Google Scholar
Hoffman, S. L., Rustama, D., Punjabi, N. H., Surampaet, B., Sanjaya, B., Dimpudus, A. J., Mckee, K. T. Jr., Paleologo, F. P., Campbell, J. R., Marwoto, H. and Laughlin, L. (1988). High-dose dexamethasone in quinine-treated patients with cerebral malaria: a double-blind, placebo-controlled trial. Journal of Infectious Diseases 158, 325331.Google Scholar
Hunt, N. H., Golenser, J., Chan-Ling, T., Parekh, S., Rae, C., Potter, S., Medana, I. M., Miu, J. and Ball, H. J. (2006). Immunopathogenesis of cerebral malaria. International Journal for Parasitology 36, 569582.Google Scholar
Hviid, L., Kurtzhals, J. A., Goka, B. Q., Oliver-Commey, J. O., Nkrumah, F. K. and Theander, T. G. (1997). Rapid reemergence of T cells into peripheral circulation following treatment of severe and uncomplicated Plasmodium falciparum malaria. Infection and Immunity 65, 40904093.CrossRefGoogle ScholarPubMed
Ibiwoye, M. O., Howard, C. V., Sibbons, P., Hasan, M. and Van Velzen, D. (1993). Cerebral malaria in the rhesus monkey (Macaca mulatta): observations on host pathology. Journal of Comparative Pathology 108, 303310.Google Scholar
Idro, R., Jenkins, N. E. and Newton, C. R. (2005). Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurology 4, 827840.Google Scholar
Janssen, C. S., Barrett, M. P., Turner, C. M. and Phillips, R. S. (2002). A large gene family for putative variant antigens shared by human and rodent malaria parasites. Proceedings of the Royal Society of London, B 269, 431436.Google Scholar
Jennings, V. M., Lal, A. A. and Hunter, R. L. (1998). Evidence for multiple pathologic and protective mechanisms of murine cerebral malaria. Infection and Immunity 66, 59725979.Google Scholar
Jensen, A. T., Magistrado, P., Sharp, S., Joergensen, L., Lavstsen, T., Chiucchiuini, A., Salanti, A., Vestergaard, L. S., Lusingu, J. P., Hermsen, R., Sauerwein, R., Christensen, J., Nielsen, M. A., Hviid, L., Sutherland, C., Staalsoe, T. and Theander, T. G. (2004). Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. Journal of Experimental Medicine 199, 11791190.Google Scholar
John, C. C., Panoskaltsis-Mortari, A., Opoka, R. O., Park, G. S., Orchard, P. J., Jurek, A. M., Idro, R., Byarugaba, J. and Boivin, M. J. (2008). Cerebrospinal fluid cytokine levels and cognitive impairment in cerebral malaria. American Journal of Tropical Medicine and Hygiene 78, 198205.Google Scholar
Johnson, J. K., Swerlick, R. A., Grady, K. K., Millet, P. and Wick, T. M. (1993). Cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelium is regulatable by cytokines and phorbol ester. Journal of Infectious Diseases 167, 698703.Google Scholar
Kaiser, K., Texier, A., Ferrandiz, J., Buguet, A., Meiller, A., Latour, C., Peyron, F., Cespuglio, R. and Picot, S. (2006). Recombinant human erythropoietin prevents the death of mice during cerebral malaria. Journal of Infectious Diseases 193, 987995.Google Scholar
Kampfl, A. W., Birbamer, G. G., Pfausler, B. E., Haring, H. P. and Schmutzhard, E. (1993). Isolated pontine lesion in algid cerebral malaria: clinical features, management, and magnetic resonance imaging findings. American Journal of Tropical Medicine and Hygiene 48, 818822.Google Scholar
Kaul, D. K., Nagel, R. L., Llena, J. F. and Shear, H. L. (1994). Cerebral malaria in mice: demonstration of cytoadherence of infected red blood cells and microrheologic correlates. American Journal of Tropical Medicine and Hygiene 50, 512521.CrossRefGoogle ScholarPubMed
Knight, J. C., Udalova, I., Hill, A. V., Greenwood, B. M., Peshu, N., Marsh, K. and Kwiatkowski, D. (1999). A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nature Genetics 22, 145150.CrossRefGoogle Scholar
Koch, O., Awomoyi, A., Usen, S., Jallow, M., Richardson, A., Hull, J., Pinder, M., Newport, M. and Kwiatkowski, D. (2002). IFNGR1 gene promoter polymorphisms and susceptibility to cerebral malaria. Journal of Infectious Diseases 185, 16841687.Google Scholar
Kossodo, S., Monso, C., Juillard, P., Velu, T., Goldman, M. and Grau, G. E. (1997). Interleukin-10 modulates susceptibility in experimental cerebral malaria. Immunology 91, 536540.Google Scholar
Kremsner, P. G., Grundmann, H., Neifer, S., Sliwa, K., Sahlmuller, G., Hegenscheid, B. and Bienzle, U. (1991). Pentoxifylline prevents murine cerebral malaria. Journal of Infectious Diseases 164, 605608.Google Scholar
Lackner, P., Beer, R., Helbok, R., Broessner, G., Engelhardt, K., Brenneis, C., Schmutzhard, E. and Pfaller, K. (2006). Scanning electron microscopy of the neuropathology of murine cerebral malaria. Malaria Journal 5, 116.CrossRefGoogle ScholarPubMed
Li, J., Chang, W. L., Sun, G., Chen, H. L., Specian, R. D., Berney, S. M., Kimpel, D., Granger, D. N. and Van Der Heyde, H. C. (2003). Intercellular adhesion molecule 1 is important for the development of severe experimental malaria but is not required for leukocyte adhesion in the brain. Journal of Investigative Medicine 51, 128140.CrossRefGoogle Scholar
Loizon, S., Boeuf, P., Tetteh, J. K., Goka, B., Obeng-Adjei, G., Kurtzhals, J. A., Rogier, C., Akanmori, B. D., Mercereau-Puijalon, O., Hviid, L. and Behr, C. (2007). V beta profiles in African children with acute cerebral or uncomplicated malaria: very focused changes among a remarkable global stability. Microbes and Infection 9, 12521259.Google Scholar
Lou, J., Gasche, Y., Zheng, L., Critico, B., Monso-Hinard, C., Juillard, P., Morel, P., Buurman, W. A. and Grau, G. E. (1998). Differential reactivity of brain microvascular endothelial cells to TNF reflects the genetic susceptibility to cerebral malaria. European Journal of Immunology 28, 39894000.3.0.CO;2-X>CrossRefGoogle Scholar
Lou, J., Lucas, R. and Grau, G. E. (2001). Pathogenesis of cerebral malaria: recent experimental data and possible applications for humans. Clinical Microbiology Reviews 14, 810820.CrossRefGoogle ScholarPubMed
Lovegrove, F. E., Gharib, S. A., Patel, S. N., Hawkes, C. A., Kain, K. C. and Liles, W. C. (2007). Expression microarray analysis implicates apoptosis and interferon-responsive mechanisms in susceptibility to experimental cerebral malaria. American Journal of Pathology 171, 18941903.Google Scholar
Lovegrove, F. E., Gharib, S. A., Pena-Castillo, L., Patel, S. N., Ruzinski, J. T., Hughes, T. R., Liles, W. C. and Kain, K. C. (2008). Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model. PLoS Pathogens 4, e1000068.Google Scholar
Lundie, R. J., De Koning-Ward, T. F., Davey, G. M., Nie, C. Q., Hansen, D. S., Lau, L. S., Mintern, J. D., Belz, G. T., Schofield, L., Carbone, F. R., Villadangos, J. A., Crabb, B. S. and Heath, W. R. (2008). Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8alpha+ dendritic cells. Proceedings of the National Academy of Sciences, USA 105, 1450914514.CrossRefGoogle ScholarPubMed
Mangano, V. D., Clark, T. G., Auburn, S., Campino, S., Diakite, M., Fry, A. E., Green, A., Richardson, A., Jallow, M., Sisay-Joof, F., Pinder, M., Griffiths, M. J., Newton, C., Peshu, N., Williams, T. N., Marsh, K., Molyneux, M. E., Taylor, T. E., Modiano, D., Kwiatkowski, D. P. and Rockett, K. A. (2009). Lack of association of interferon regulatory factor 1 with severe malaria in affected child-parental trio studies across three African populations. PLoS One 4, e4206.Google Scholar
Mangano, V. D., Luoni, G., Rockett, K. A., Sirima, B. S., Konate, A., Forton, J., Clark, T. G., Bancone, G., Sadighi Akha, E., Kwiatkowski, D. P. and Modiano, D. (2008). Interferon regulatory factor-1 polymorphisms are associated with the control of Plasmodium falciparum infection. Genes & Immunity 9, 122129.Google Scholar
Marsh, K. and Snow, R. W. (1999). Malaria transmission and morbidity. Parassitologia 41, 241246.Google Scholar
McCormick, C. J., Craig, A., Roberts, D., Newbold, C. I. and Berendt, A. R. (1997). Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. The Journal of Clinical Investigation 100, 25212529.Google Scholar
McLean, S. A., Pearson, C. D. and Phillips, R. S. (1986). Antigenic variation in Plasmodium chabaudi: analysis of parent and variant populations by cloning. Parasite Immunology 8, 415424.Google Scholar
Medana, I. M., Hunt, N. H. and Chan-Ling, T. (1997 a). Early activation of microglia in the pathogenesis of fatal murine cerebral malaria. Glia 19, 91103.Google Scholar
Medana, I. M., Hunt, N. H. and Chaudhri, G. (1997 b). Tumor necrosis factor-alpha expression in the brain during fatal murine cerebral malaria: evidence for production by microglia and astrocytes. American Journal of Pathology 150, 14731486.Google Scholar
Mishra, S. K. and Wiese, L. (2009). Advances in the management of cerebral malaria in adults. Current Opinion in Neurology 22, 302307.Google Scholar
Mitchell, A. J., Hansen, A. M., Hee, L., Ball, H. J., Potter, S. M., Walker, J. C. and Hunt, N. H. (2005). Early cytokine production is associated with protection from murine cerebral malaria. Infection and Immunity 73, 56455653.Google Scholar
Miu, J., Mitchell, A. J., Muller, M., Carter, S. L., Manders, P. M., McQuillan, J. A., Saunders, B. M., Ball, H. J., Lu, B., Campbell, I. L. and Hunt, N. H. (2008). Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. Journal of Immunology 180, 12171230.CrossRefGoogle ScholarPubMed
Miyakoda, M., Kimura, D., Yuda, M., Chinzei, Y., Shibata, Y., Honma, K. and Yui, K. (2008). Malaria-specific and nonspecific activation of CD8+ T cells during blood stage of Plasmodium berghei infection. Journal of Immunology 181, 14201428.Google Scholar
Molyneux, M. E., Taylor, T. E., Wirima, J. J. and Borgstein, A. (1989). Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Quarterly Journal of Medicine 71, 441459.Google Scholar
Monso-Hinard, C., Lou, J. N., Behr, C., Juillard, P. and Grau, G. E. (1997). Expression of major histocompatibility complex antigens on mouse brain microvascular endothelial cells in relation to susceptibility to cerebral malaria. Immunology 92, 5359.Google Scholar
Nagayasu, E., Nagakura, K., Akaki, M., Tamiya, G., Makino, S., Nakano, Y., Kimura, M. and Aikawa, M. (2002). Association of a determinant on mouse chromosome 18 with experimental severe Plasmodium berghei malaria. Infection and Immunity 70, 512516.Google Scholar
Neill, A. L. and Hunt, N. H. (1995). Effects of endotoxin and dexamethasone on cerebral malaria in mice. Parasitology 111, 443454.Google Scholar
Newbold, C., Craig, A., Kyes, S., Rowe, A., Fernandez-Reyes, D. and Fagan, T. (1999). Cytoadherence, pathogenesis and the infected red cell surface in Plasmodium falciparum. International Journal for Parasitology 29, 927937.Google Scholar
Nie, C. Q., Bernard, N. J., Norman, M. U., Amante, F. H., Lundie, R. J., Crabb, B. S., Heath, W. R., Engwerda, C. R., Hickey, M. J., Schofield, L. and Hansen, D. S. (2009). IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection. PLoS Pathogens 5, e1000369.Google Scholar
Nie, C. Q., Bernard, N. J., Schofield, L. and Hansen, D. S. (2007). CD4+ CD25+ regulatory T cells suppress CD4+ T-cell function and inhibit the development of Plasmodium berghei-specific TH1 responses involved in cerebral malaria pathogenesis. Infection and Immunity 75, 22752282.Google Scholar
Nitcheu, J., Bonduelle, O., Combadiere, C., Tefit, M., Seilhean, D., Mazier, D. and Combadiere, B. (2003). Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis. Journal of Immunology 170, 22212228.Google Scholar
Normark, J., Nilsson, D., Ribacke, U., Winter, G., Moll, K., Wheelock, C. E., Bayarugaba, J., Kironde, F., Egwang, T. G., Chen, Q., Andersson, B. and Wahlgren, M. (2007). PfEMP1-DBL1alpha amino acid motifs in severe disease states of Plasmodium falciparum malaria. Proceedings of the National Academy of Sciences, USA 104, 1583515840.Google Scholar
Oakley, M. S., McCutchan, T. F., Anantharaman, V., Ward, J. M., Faucette, L., Erexson, C., Mahajan, B., Zheng, H., Majam, V., Aravind, L. and Kumar, S. (2008). Host biomarkers and biological pathways that are associated with the expression of experimental cerebral malaria in mice. Infection and Immunity 76, 45184529.Google Scholar
Ockenhouse, C. F., Ho, M., Tandon, N. N., Van Seventer, G. A., Shaw, S., White, N. J., Jamieson, G. A., Chulay, J. D. and Webster, H. K. (1991). Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. Journal of Infectious Diseases 164, 163169.Google Scholar
Ockenhouse, C. F., Tandon, N. N., Magowan, C., Jamieson, G. A. and Chulay, J. D. (1989). Identification of a platelet membrane glycoprotein as a falciparum malaria sequestration receptor. Science 243, 14691471.Google Scholar
Ockenhouse, C. F., Tegoshi, T., Maeno, Y., Benjamin, C., Ho, M., Kan, K. E., Thway, Y., Win, K., Aikawa, M. and Lobb, R. R. (1992). Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. Journal of Experimental Medicine 176, 11831189.Google Scholar
Ohno, T. and Nishimura, M. (2004). Detection of a new cerebral malaria susceptibility locus, using CBA mice. Immunogenetics 56, 675678.CrossRefGoogle ScholarPubMed
Oleinikov, A. V., Amos, E., Frye, I. T., Rossnagle, E., Mutabingwa, T. K., Fried, M. and Duffy, P. E. (2009). High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies. PLoS Pathogens 5, e1000386.Google Scholar
Ortolano, F., Maffia, P., Dever, G., Hutchison, S., Benson, R., Millington, O. R., De Simoni, M. G., Bushell, T. J., Garside, P., Carswell, H. V. and Brewer, J. M. (2009). Imaging T-cell movement in the brain during experimental cerebral malaria. Parasite Immunology 31, 147150.Google Scholar
Pais, T. F. and Chatterjee, S. (2005). Brain macrophage activation in murine cerebral malaria precedes accumulation of leukocytes and CD8+ T cell proliferation. Journal of Neuroimmunology 163, 7383.Google Scholar
Pamplona, A., Ferreira, A., Balla, J., Jeney, V., Balla, G., Epiphanio, S., Chora, A., Rodrigues, C. D., Gregoire, I. P., Cunha-Rodrigues, M., Portugal, S., Soares, M. P. and Mota, M. M. (2007). Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nature Medicine 13, 703710.Google Scholar
Patankar, T. F., Karnad, D. R., Shetty, P. G., Desai, A. P. and Prasad, S. R. (2002). Adult cerebral malaria: prognostic importance of imaging findings and correlation with postmortem findings. Radiology 224, 811816.Google Scholar
Patnaik, J. K., Das, B. S., Mishra, S. K., Mohanty, S., Satpathy, S. K. and Mohanty, D. (1994). Vascular clogging, mononuclear cell margination, and enhanced vascular permeability in the pathogenesis of human cerebral malaria. American Journal of Tropical Medicine and Hygiene 51, 642647.Google Scholar
Penet, M. F., Kober, F., Confort-Gouny, S., Le Fur, Y., Dalmasso, C., Coltel, N., Liprandi, A., Gulian, J. M., Grau, G. E., Cozzone, P. J. and Viola, A. (2007). Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA. Journal of Biological Chemistry 282, 1450514514.Google Scholar
Penet, M. F., Viola, A., Confort-Gouny, S., Le Fur, Y., Duhamel, G., Kober, F., Ibarrola, D., Izquierdo, M., Coltel, N., Gharib, B., Grau, G. E. and Cozzone, P. J. (2005). Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema. Journal of Neuroscience 25, 73527358.Google Scholar
Potter, S., Chan-Ling, T., Ball, H. J., Mansour, H., Mitchell, A., Maluish, L. and Hunt, N. H. (2006). Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. International Journal for Parasitology 36, 485496.Google Scholar
Rae, C., Mcquillan, J. A., Parekh, S. B., Bubb, W. A., Weiser, S., Balcar, V. J., Hansen, A. M., Ball, H. J. and Hunt, N. H. (2004). Brain gene expression, metabolism, and bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria. FASEB Journal 18, 499510.Google Scholar
Randall, L. M., Amante, F. H., Mcsweeney, K. A., Zhou, Y., Stanley, A. C., Haque, A., Jones, M. K., Hill, G. R., Boyle, G. M. and Engwerda, C. R. (2008 a). Common strategies to prevent and modulate experimental cerebral malaria in mouse strains with different susceptibilities. Infection and Immunity 76, 33123320.Google Scholar
Randall, L. M., Amante, F. H., Zhou, Y., Stanley, A. C., Haque, A., Rivera, F., Pfeffer, K., Scheu, S., Hill, G. R., Tamada, K. and Engwerda, C. R. (2008 b). Cutting edge: selective blockade of LIGHT-lymphotoxin beta receptor signaling protects mice from experimental cerebral malaria caused by Plasmodium berghei ANKA. Journal of Immunology 181, 74587462.Google Scholar
Reader, J. C., Cowman, A. F., Davern, K. M., Beeson, J. G., Thompson, J. K., Rogerson, S. J. and Brown, G. V. (1999). The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by P. falciparum erythrocyte membrane protein 1. Proceedings of the National Academy of Sciences, USA 90, 51985202.Google Scholar
Renia, L., Potter, S. M., Mauduit, M., Rosa, D. S., Kayibanda, M., Deschemin, J. C., Snounou, G. and Gruner, A. C. (2006). Pathogenic T cells in cerebral malaria. International Journal for Parasitology 36, 547554.Google Scholar
Rest, J. R. (1982). Cerebral malaria in inbred mice. I. A new model and its pathology. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 410415.Google Scholar
Rogerson, S. J., Tembenu, R., Dobano, C., Plitt, S., Taylor, T. E. and Molyneux, M. E. (1999). Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria. American Journal of Tropical Medicine and Hygiene 61, 467472.Google Scholar
Rudin, W., Eugster, H. P., Bordmann, G., Bonato, J., Muller, M., Yamage, M. and Ryffel, B. (1997). Resistance to cerebral malaria in tumor necrosis factor-alpha/beta-deficient mice is associated with a reduction of intercellular adhesion molecule-1 up-regulation and T helper type 1 response. American Journal of Pathology 150, 257266.Google Scholar
Saeftel, M., Krueger, A., Arriens, S., Heussler, V., Racz, P., Fleischer, B., Brombacher, F. and Hoerauf, A. (2004). Mice deficient in interleukin-4 (IL-4) or IL-4 receptor alpha have higher resistance to sporozoite infection with Plasmodium berghei (ANKA) than do naive wild-type mice. Infection and Immunity 72, 322331.Google Scholar
Salanti, A., Dahlback, M., Turner, L., Nielsen, M. A., Barfod, L., Magistrado, P., Jensen, A. T., Lavstsen, T., Ofori, M. F., Marsh, K., Hviid, L. and Theander, T. G. (2004). Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. Journal of Experimental Medicine 200, 11971203.Google Scholar
Schaeffer, M., Han, S. J., Chtanova, T., Van Dooren, G. G., Herzmark, P., Chen, Y., Roysam, B., Striepen, B. and Robey, E. A. (2009). Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii. Journal of Immunology 182, 63796393.CrossRefGoogle ScholarPubMed
Scherf, A., Lopez-Rubio, J. J. and Riviere, L. (2008). Antigenic variation in Plasmodium falciparum. Annual Review of Microbiology 62, 445470.Google Scholar
Schluesener, H. J., Kremsner, P. G. and Meyermann, R. (1998). Widespread expression of MRP8 and MRP14 in human cerebral malaria by microglial cells. Acta Neuropathologica 96, 575580.Google Scholar
Schofield, L. and Grau, G. E. (2005). Immunological processes in malaria pathogenesis. Nature Reviews Immunology 5, 722735.Google Scholar
Schofield, L., Novakovic, S., Gerold, P., Schwarz, R. T., McConville, M. J. A and Tachado, S. D. (1996). Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. Journal of Immunology 156, 18861896.Google Scholar
Seydel, K. B., Milner, D. A. Jr., Kamiza, S. B., Molyneux, M. E. and Taylor, T. E. (2006). The distribution and intensity of parasite sequestration in Comatose Malawian Children. Journal of Infectious Diseases 194, 205208.Google Scholar
Silamut, K., Phu, N. H., Whitty, C., Turner, G. D., Louwrier, K., Mai, N. T., Simpson, J. A., Hien, T. T. and White, N. J. (1999). A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. American Journal of Pathology 155, 395410.CrossRefGoogle ScholarPubMed
Smith, J. D., Craig, A. G., Kriek, N., Hudson-Taylor, D., Kyes, S., Fagan, T., Pinches, R., Baruch, D. I., Newbold, C. I. and Miller, L. H. (2000). Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proceedings of the National Academy of Sciences, USA 97, 17661771.Google Scholar
Srivastava, K., Cockburn, I. A., Swaim, A., Thompson, L. E., Tripathi, A., Fletcher, C. A., Shirk, E. M., Sun, H., Kowalska, M. A., Fox-Talbot, K., Sullivan, D., Zavala, F. and Morrell, C. N. (2008). Platelet factor 4 mediates inflammation in experimental cerebral malaria. Cell Host & Microbe 4, 179187.Google Scholar
Taylor, T. E., Fu, W. J., Carr, R. A., Whitten, R. O., Mueller, J. S., Fosiko, N. G., Lewallen, S., Liomba, N. G. and Molyneux, M. E. (2004). Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nature Medicine 10, 143145.Google Scholar
Teasdale, G. and Jennett, B. (1974). Assessment of coma and impaired consciousness. A practical scale. Lancet 2, 8184.Google Scholar
Togbe, D., De Sousa, P. L., Fauconnier, M., Boissay, V., Fick, L., Scheu, S., Pfeffer, K., Menard, R., Grau, G. E., Doan, B. T., Beloeil, J. C., Renia, L., Hansen, A. M., Ball, H. J., Hunt, N. H., Ryffel, B. and Quesniaux, V. F. (2008). Both functional LTbeta receptor and TNF receptor 2 are required for the development of experimental cerebral malaria. PLoS One 3, e2608.Google Scholar
Tripathi, A. K., Sha, W., Shulaev, V., Stins, M. F. and Sullivan, D. J. Jr. (2009). Plasmodium falciparum infected erythrocytes induce NF-{kappa}B regulated inflammatory pathways in human cerebral endothelium. Blood 114, 42344252.Google Scholar
Turner, G. D., Morrison, H., Jones, M., Davis, T. M., Looareesuwan, S., Buley, I. D., Gatter, K. C., Newbold, C. I., Pukritayakamee, S., Nagachinta, B. and et al. (1994). An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. American Journal of Pathology 145, 10571069.Google Scholar
Udomsangpetch, R., Pipitaporn, B., Silamut, K., Pinches, R., Kyes, S., Looareesuwan, S., Newbold, C. and White, N. J. (2002). Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes. Proceedings of the National Academy of Sciences, USA 99, 1182511829.Google Scholar
Udomsangpetch, R., Reinhardt, P. H., Schollaardt, T., Elliott, J. F., Kubes, P. and Ho, M. (1997). Promiscuity of clinical Plasmodium falciparum isolates for multiple adhesion molecules under flow conditions. Journal of Immunology 158, 43584364.Google Scholar
Udomsangpetch, R., Taylor, B. J., Looareesuwan, S., White, N. J., Elliott, J. F. and Ho, M. (1996). Receptor specificity of clinical Plasmodium falciparum isolates: nonadherence to cell-bound E-selectin and vascular cell adhesion molecule-1. Blood 88, 27542760.Google Scholar
Van Den Steen, P. E., Deroost, K., Van Aelst, I., Geurts, N., Martens, E., Struyf, S., Nie, C. Q., Hansen, D. S., Matthys, P., Van Damme, J. and Opdenakker, G. (2008). CXCR3 determines strain susceptibility to murine cerebral malaria by mediating T lymphocyte migration toward IFN-gamma-induced chemokines. European Journal of Immunology 38, 10821095.Google Scholar
Van Der Heyde, H. C., Nolan, J., Combes, V., Gramaglia, I. and Grau, G. E. (2006). A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends in Parasitology 22, 503508.CrossRefGoogle ScholarPubMed
Van Hensbroek, M. B., Palmer, A., Onyiorah, E., Schneider, G., Jaffar, S., Dolan, G., Memming, H., Frenkel, J., Enwere, G., Bennett, S., Kwiatkowski, D. and Greenwood, B. (1996). The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. Journal of Infectious Diseases 174, 10911097.Google Scholar
Verra, F., Mangano, V. D. and Modiano, D. (2009). Genetics of susceptibility to Plasmodium falciparum: from classical malaria resistance genes towards genome-wide association studies. Parasite Immunology 31, 234253.Google Scholar
Von Zur Muhlen, C., Sibson, N. R., Peter, K., Campbell, S. J., Wilainam, P., Grau, G. E., Bode, C., Choudhury, R. P. and Anthony, D. C. (2008). A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI. The Journal of Clinical Investigation 118, 11981207.Google Scholar
Walther, M., Jeffries, D., Finney, O. C., Njie, M., Ebonyi, A., Deininger, S., Lawrence, E., Ngwa-Amambua, A., Jayasooriya, S., Cheeseman, I. H., Gomez-Escobar, N., Okebe, J., Conway, D. J. and Riley, E. M. (2009). Distinct roles for FOXP3 and FOXP3 CD4 T cells in regulating cellular immunity to uncomplicated and severe Plasmodium falciparum malaria. PLoS Pathogens 5, e1000364.Google Scholar
Wassmer, S. C., Combes, V. and Grau, G. E. (2003). Pathophysiology of cerebral malaria: role of host cells in the modulation of cytoadhesion. Annals of the New York Academy of Science 992, 3038.Google Scholar
Wassmer, S. C., De Souza, J. B., Frere, C., Candal, F. J., Juhan-Vague, I. and Grau, G. E. (2006). TGF-beta1 released from activated platelets can induce TNF-stimulated human brain endothelium apoptosis: a new mechanism for microvascular lesion during cerebral malaria. Journal of Immunology 176, 11801184.Google Scholar
Wassmer, S. C., Lepolard, C., Traore, B., Pouvelle, B., Gysin, J. and Grau, G. E. (2004). Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. Journal of Infectious Diseases 189, 180189.Google Scholar
Weiser, S., Miu, J., Ball, H. J. and Hunt, N. H. (2007). Interferon-gamma synergises with tumour necrosis factor and lymphotoxin-alpha to enhance the mRNA and protein expression of adhesion molecules in mouse brain endothelial cells. Cytokine 37, 8491.Google Scholar
White, V. A., Lewallen, S., Beare, N. A., Molyneux, M. E. and Taylor, T. E. (2009). Retinal pathology of pediatric cerebral malaria in Malawi. PLoS One 4, e4317.Google Scholar
Wilson, E. H., Harris, T. H., Mrass, P., John, B., Tait, E. D., Wu, G. F., Pepper, M., Wherry, E. J., Dzierzinski, F., Roos, D., Haydon, P. G., Laufer, T. M., Weninger, W. and Hunter, C. A. (2009). Behavior of parasite-specific effector CD8+ T cells in the brain and visualization of a kinesis-associated system of reticular fibers. Immunity 30, 300311.Google Scholar
Yanez, D. M., Manning, D. D., Cooley, A. J., Weidanz, W. P. and Van Der Heyde, H. C. (1996). Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria. Journal of Immunology 157, 16201624.Google Scholar
Yeo, T. W., Lampah, D. A., Gitawati, R., Tjitra, E., Kenangalem, E., McNeil, Y. R., Darcy, C. J., Granger, D. L., Weinberg, J. B., Lopansri, B. K., Price, R. N., Duffull, S. B., Celermajer, D. S. and Anstey, N. M. (2007). Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. Journal of Experimental Medicine 204, 26932704.Google Scholar
Yeo, T. W., Lampah, D. A., Gitawati, R., Tjitra, E., Kenangalem, E., McNeil, Y. R., Darcy, C. J., Granger, D. L., Weinberg, J. B., Lopansri, B. K., Price, R. N., Duffull, S. B., Celermajer, D. S. and Anstey, N. M. (2008). Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations. Journal of Infectious Diseases 198, 602608.Google Scholar
Yipp, B. G., Anand, S., Schollaardt, T., Patel, K. D., Looareesuwan, S. and Ho, M. (2000). Synergism of multiple adhesion molecules in mediating cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelial cells under flow. Blood 96, 22922298.Google Scholar
Yoeli, M. and Hargreaves, B. J. (1974). Brain capillary blockage produced by a virulent strain of rodent malaria. Science 184, 572573.Google Scholar