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Heterologous immunity revisited

Published online by Cambridge University Press:  08 June 2007

I. A. CLARK
I. A. CLARK
Affiliation:
Division of Biochemistry and Molecular Biology, School of Life Sciences, Australian National University, Canberra, Australia ACT 0200
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Abstract

Heterologous immunity, or protection by one invading organism against another across phylogenetic divides, has been recognised for decades. It was initially thought to operate largely through enhancement of phagocytosis, but this explanation became untenable when it was realised it worked extremely well against intraerythrocytic protozoa and killed them while they were free in the circulation. Clearly a soluble mediator was called for. This review summarises the logic that arose from this observation, which led to a wider appreciation of the roles of pro-inflammatory cytokines, and then nitric oxide, in the host's response against invaders, as well as the ability of these mediators to harm the host itself if they are generated too enthusiastically. This has led to a discernable pattern across heterologous immunity as a whole, and its lessons influence a range of areas, including vaccine development.

Keywords

BCGBabesiamalariaTNFnitric oxidedisease pathogenesisvaccines
Type
Research Article
Information
Parasitology , Volume 122 , Supplement S1 , March 2001 , pp. S51 - S59
Copyright
© 2002 Cambridge University Press

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References

AHMED, K., AL MATROUK, K. A., MARTINEZ, G., OISHI, K., ROTIMI, V. O. & NAGATAKE, T. (1999). Increased serum levels of interferon-gamma and interleukin-12 during human brucellosis. American Journal of Tropical Medicine and Hygiene 61, 425–427.CrossRefGoogle Scholar
AL YAMAN, F., GENTON, B., MOKELA, D., ROCKETT, K. A., ALPERS, M. P. & CLARK, I. A. (1996). Association between serum levels of reactive nitrogen intermediates and coma in children with cerebral malaria in Papua New Guinea. Transactions of the Royal Society of Tropical Medicine and Hygiene 90, 270–273.CrossRefGoogle Scholar
AMMAH, A., NKUO, A. T., NDIP, R. & DEAS, J. E. (1999). An update on concurrent malaria and typhoid fever in Cameroon. Transactions of the Royal Society of Tropical Medicine and Hygiene 93, 127–129.CrossRefGoogle Scholar
ANSTEY, N. M., WEINBERG, J. B., HASSANALI, M., MWAIKAMBO, E. D., MANYENGA, D., MISUKONIS, M. A., ARNELLE, D. R., HOLLIS, D., MCDONALD, M. I. & GRANGER, D. L. (1996). Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. Journal of Experimental Medicine 184, 557–567.CrossRefGoogle Scholar
ARSENIJEVIC, D., GIRARDIER, L., SEYDOUX, J., CHANG, H. R. & DULLOO, A. G. (1997). Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii. American Journal of Physiology 272, E908–E917.CrossRefGoogle Scholar
BERMUDEZ, L. E. (1993). Differential mechanisms of intracellular killing of Mycobacterium avium and Listeria monocytogenes by activated human and murine macrophages. The role of nitric oxide. Clinical and Experimental Immunology 91, 277–281.CrossRefGoogle Scholar
BERMUDEZ, L. E. & YOUNG, L. S. (1988). Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex. Journal of Immunology 140, 3006–3013.Google Scholar
BHUTTA, Z. A., MANSOORALI, N. & HUSSAIN, R. (1997). Plasma cytokines in paediatric typhoidal salmonellosis: correlation with clinical course and outcome. Journal of Infection 35, 253–256.CrossRefGoogle Scholar
BLOOM, B. R., MAZZACCARO, R. J., FLYNN, J. A., CHAN, J., SOUSA, A., SALGAME, P., STENGER, S., MODLIN, R. L., KRENSKY, A., DEMANT, P. & KRAMNI, I. (1999). Immunology of an infectious disease: Pathogenesis and protection in tuberculosis. Immunologist 7, 54–59.Google Scholar
BURGNER, D., XU, W. M., ROCKETT, K., GRAVENOR, M., CHARLES, I. G., HILL, A. V.S. & KWIATKOWSKI, D. (1998). Inducible nitric oxide synthase polymorphism and fatal cerebral malaria. Lancet 352, 1193–1194.CrossRefGoogle Scholar
BUTCHER, G. A., GARLAND, T., ADJUKIEWICZ, A. B. & CLARK, I. A. (1990). Serum TNF associated with malaria in patients in the Solomon Islands. Transactions of the Royal Society of Tropical Medicine and Hygiene 85, 658–661.CrossRefGoogle Scholar
CARSWELL, E. A., OLD, L. J., KASSEL, R. L., GREEN, S., FIORE, N. & WILLIAMSON, B. (1975). An endotoxin induced serum factor that causes necrosis of tumors. Proceedings of the National Academy of Sciences, USA 72, 3666–3670.CrossRefGoogle Scholar
CHANG, H. R., GRAU, G. E. & PERCHERE, J. C. (1990). Role of TNF and IL-1 in infections with Toxoplasma gondii. Immunology 69, 33–37.Google Scholar
CHAO, C. C., ANDERSON, W. R., HU, S., GEKKER, G., MARTELLA, A. & PETERSON, P. K. (1993). Activated microglia inhibit multiplication of Toxoplasma gondii via a nitric oxide mechanism. Clinical Immunology and Immunopathology 67, 178–183.CrossRefGoogle Scholar
CLARK, I. A. (1978). Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis? Lancet ii, 75–77.Google Scholar
CLARK, I. A. (1979a). Protection of mice against Babesia microti with cord factor, COAM, zymosan, glucan, Salmonella and Listeria. Parasite Immunology 1, 179–196.Google Scholar
CLARK, I. A. (1979b). Resistance to Babesia spp. and Plasmodium sp. in mice pretreated with an extract of Coxiella burnetii. Infection and Immunity 24, 319–325.Google Scholar
CLARK, I. A. (1982a). Correlation between susceptibility to malaria and babesia parasites and to endotoxin. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 4–7.Google Scholar
CLARK, I. A. (1982b). Suggested importance of monokines in pathophysiology of endotoxin shock and malaria. Klinische Wochenschrift 60, 756–758.Google Scholar
CLARK, I. A. (1987a). Cell-mediated immunity in protection and pathology of malaria. Parasitology Today 3, 300–305.Google Scholar
CLARK, I. A. (1987b). Monokines and lymphokines in malarial pathology. Annals of Tropical Medicine and Parasitology 81, 577–585.Google Scholar
CLARK, I. A., ALLISON, A. C. & COX, F. E. G. (1976). Protection of mice against Babesia and Plasmodium with BCG. Nature 259, 309–311.CrossRefGoogle Scholar
CLARK, I. A. & CHAUDHRI, G. (1988a). Tumor necrosis factor in malaria-induced abortion. American Journal of Tropical Medicine and Hygiene 39, 246–249.Google Scholar
CLARK, I. A. & CHAUDHRI, G. (1988b). Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. British Journal of Haematology 70, 99–103.Google Scholar
CLARK, I. A., CHAUDHRI, G. & COWDEN, W. B. (1989). Roles of tumour necrosis factor in the illness and pathology of malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 83, 436–440.CrossRefGoogle Scholar
CLARK, I. A., COWDEN, W. B., BUTCHER, G. A. & HUNT, N. H. (1987a). Possible roles of tumor necrosis factor in the pathology of malaria. American Journal of Pathology 129, 192–199.Google Scholar
CLARK, I. A., COX, F. E. G. & ALLISON, A. C. (1977a). Protection of mice against Babesia spp. and Plasmodium spp. with killed Corynebacterium parvum. Parasitology 74, 9–18.Google Scholar
CLARK, I. A., HUNT, N. H., BUTCHER, G. A. & COWDEN, W. B. (1987b). Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. Journal of Immunology 139, 3493–3496.Google Scholar
CLARK, I. A., MACMICKING, J. D., GRAY, K. M., ROCKETT, K. A. & COWDEN, W. B. (1992a). Malaria mimicry with tumor necrosis factor – contrasts between species of murine malaria and Plasmodium falciparum. American Journal of Pathology 140, 325–336.Google Scholar
CLARK, I. A., RICHMOND, J. E., WILLS, E. J. & ALLISON, A. C. (1975). Immunity to intra-erythrocytic protozoa. Lancet ii, 1128–1129.CrossRefGoogle Scholar
CLARK, I. A., ROCKETT, K. A. & COWDEN, W. B. (1991). Proposed link between cytokines, nitric oxide, and human cerebral malaria. Parasitology Today 7, 205–207.CrossRefGoogle Scholar
CLARK, I. A., ROCKETT, K. A. & COWDEN, W. B. (1992b). Possible central role of nitric oxide in conditions clinically similar to cerebral malaria. Lancet 340, 894–896.Google Scholar
CLARK, I. A., VIRELIZIER, J.-L., CARSWELL, E. A. & WOOD, P. R. (1981). Possible importance of macrophage-derived mediators in acute malaria. Infection and Immunity 32, 1058–1066.Google Scholar
CLARK, I. A., WILLS, E. J., RICHMOND, J. E. & ALLISON, A. C. (1977b). Suppression of babesiosis in BCG-infected mice and its correlation with tumor inhibition. Infection and Immunity 17, 430–438.Google Scholar
COLLINS, F. M. & SCOTT, M. T. (1974). Effect of Corynebacterium parvum on the growth of Salmonella enteritidis in mice. Infection and Immunity 9, 863–869.Google Scholar
COT, S., RINGWALD, P., MULDER, B., MIAILHES, P., YAPYAP, J., NUSSLER, A. K. & ELING, W. M. C. (1994). Nitric oxide in cerebral malaria. Journal of Infectious Diseases 169, 1417–1418.CrossRefGoogle Scholar
COX, F. E. G. (1970). Protective immunity between malaria parasites and piroplasms in mice. Bulletin of the World Health Organisation 43, 325–336.Google Scholar
COX, F. E. G. (1978). Heterologous immunity between piroplasms and malaria parasites: the simultaneous elimination of Plasmodium vinckei and Babesia microti from the blood of doubly infected mice. Parasitology 76, 55–60.CrossRefGoogle Scholar
CREAGAN, E. T., KOVACH, J. S., MOERTEL, C. G., FRYTAK, S. & KVOLS, L. K. (1988). A phase 1 clinical trial of recombinant human tumor necrosis factor. Cancer 62, 2467–2471.3.0.CO;2-5>CrossRefGoogle Scholar
DEGRE, M. & BUKHOLM, G. (1990). Effect of tumor necrosis factor-alpha on infection with Salmonella typhimurium in a mouse model. Journal of Biological Regulators and Homeostatic Agents 4, 157–161.Google Scholar
DELLACASAGRANDE, J., CAPO, C., RAOULT, D. & MEGE, J. L. (1999). IFN-gamma-mediated control of Coxiella burnetii survival in monocytes: The role of cell apoptosis and TNF. Journal of Immunology 162, 2259–2265.Google Scholar
DENIS, M. (1991). Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cellular Immunology 132, 150–157.CrossRefGoogle Scholar
DONDORP, A. M., PLANCHE, T., DEBEL, E. E., ANGUS, B. J., CHOTIVANICH, K. T., SILAMUT, K., ROMIJN, J. A., RUANGVEERAYUTH, R., HOEK, F. J., KAGER, P. A., VREEKEN, J. & WHITE, N. J. (1998). Nitric oxides in plasma, urine, and cerebrospinal fluid in patients with severe falciparum malaria. American Journal of Tropical Medicine and Hygiene 59, 497–502.CrossRefGoogle Scholar
DUBOS, R. J. & SCHAEDLER, R. W. (1957). Effect of cellular constituents of Mycobacteria on the resistance of mice to heterologous infection. Journal of Experimental Medicine 106, 703–709.CrossRefGoogle Scholar
GALE, K. R., WALTISBUHL, D. J., BOWDEN, J. M., JORGENSEN, W. K., MATHESON, J., EAST, I. J., ZAKRZEWSKI, H. & LEATCH, G. (1998). Amelioration of virulent Babesia bovis infection in calves by administration of the nitric oxide synthase inhibitor aminoguanidine. Parasite Immunology 20, 441–445.CrossRefGoogle Scholar
GARTHWAITE, J., CHARLES, S. L. & CHESS-WILLIAMS, R. (1988). Endothelium-derived relaxing factor release on activation of the NMDA receptors suggests role as intercellular messenger in the brain. Nature 336, 385–388.CrossRefGoogle Scholar
GIORGIO, S., LINARES, E., CAPURRO, M. D. L., DE BIANCHI, A. G. & AUGUSTO, O. (1996). Formation of nitrosyl haemoglobin and nitrotyrosine during murine leishmaniasis. Photochemistry and Photobiology 63, 750–754.CrossRefGoogle Scholar
GRAU, G. E., FAJARDO, L. F., PIQUET, P.-F., ALLET, B., LAMBERT, P.-H. & VASSALI, P. (1987). Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237, 1210–1212.CrossRefGoogle Scholar
GRAU, G. E., TAYLOR, T. E., MOLYNEUX, M. E., WIRIMA, J. J., VASSALLI, P., HOMMEL, M. & LAMBERT, P.-H. (1989). Tumor necrosis factor and disease severity in children with falciparum malaria. New England Journal of Medicine 320, 1586–1591.CrossRefGoogle Scholar
GREEN, S., DOBRJANSKY, A., CHIASSON, M. A., CARSWELL, E., SCHWARTZ, M. K. & OLD, L J. (1977). Corynebacterium parvum as the priming agent in the production of tumor necrosis factor in the mouse. Journal of the National Cancer Institute 59, 1519–1522.CrossRefGoogle Scholar
GROSS, A., SPIESSER, S., TERRAZA, A., ROUOT, B., CARON, E. & DORNAND, J. (1998). Expression and bactericidal activity of nitric oxide synthase in Brucella suis-infected murine macrophages. Infection and Immunity 66, 1309–1316.Google Scholar
HAIDARIS, C. G., HAYNES, J. D., MELTZER, M. S. & ALLISON, A. C. (1983). Serum containing tumor necrosis factor is cytotoxic for the human malarial parasite Plasmodium falciparum. Infection and Immunity 42, 385–393.Google Scholar
HALPERN, B. N., BIOZZI, G., STIFFEL, C. & MOUTON, D. (1966). Inhibition of tumour growth by administration of killed Corynebacterium parvum. Nature 212, 853–854.CrossRefGoogle Scholar
HARDY, D. & KOTLARSKI, I. (1971). Resistance of mice to Erhlich ascites tumour after immunisation of mice with live Salmonella interitidis 11RX. Australian Journal of Experimental Biology and Medical Science 49, 271–279.CrossRefGoogle Scholar
HELMBY, H., JONSSON, G. & TROYE-BLOMBERG, M. (2000). Cellular changes and apoptosis in the spleens and peripheral blood of mice infected with blood-stage Plasmodium chabaudi chabaudi AS. Infection and Immunity 68, 1485–1490.CrossRefGoogle Scholar
HELSON, L., GREEN, S., CARSWELL, E. & OLD, L. J. (1975). Effect of tumour necrosis factor on cultured human melanoma cells. Nature 258, 731–732.CrossRefGoogle Scholar
HEROD, E., CLARK, I. A. & ALLISON, A. C. (1978). Protection of mice against the haemoprotozoan Babesia microti with Brucella abortus strain 19. Clinical and Experimental Immunology 31, 518–523.Google Scholar
HIBBS, J. B., TAINTOR, R. R., VAVRIN, Z. & RACHLIN, E. M. (1988). Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochemical and Biophysical Research Communications 157, 87–94.CrossRefGoogle Scholar
HOWARD, J. G., BIOZZI, G., HALPERN, B. N., STIFFEL, C. & MOUTON, D. (1959). The effect of Mycobacterium tuberculosis (BCG) infection on the resistance of mice to bacterial endotoxin and Salmonella enteritidis infection. British Journal of Experimental Pathology 40, 281–290.Google Scholar
JESPERSEN, A. (1976). Acquired resistance of BCG-vaccinated red mice to infection with Listeria monocytogenes. Acta Pathologica Microbiologica Scandinavica 84, 265–272.CrossRefGoogle Scholar
KELLY, M. T., GRANGER, D. L., RIBI, E., MILNER, K. C., STRAIN, S. M. & STOENNER, H. G. (1976). Tumor regression with Q fever rickettsia and a mycobacterial glycolipid. Cancer Immunology and Immunotherapy 1, 187–191.CrossRefGoogle Scholar
KERN, P., HEMMER, C. J., VAN DAMME, J., GRUSS, H.-J. & DIETRICH, M. (1989). Elevated tumour necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. American Journal of Medicine 87, 139–143.CrossRefGoogle Scholar
KHAN, I. A., SCHWARTZMAN, J. D., MATSUURA, T. & KASPER, L. H. (1997). A dichotomous role for nitric oxide during acute Toxoplasma gondii infection in mice. Proceedings of the National Academy of Sciences, USA 94, 13955–13960.CrossRefGoogle Scholar
KILBOURN, R. G., GROSS, S., JUBRAN, A., GRIFFITH, O. W., LEVI, R. & LODATO, R. F. (1990). NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proceedings of the National Academy of Sciences, USA 87, 3629–3632.CrossRefGoogle Scholar
KITCHEN, S. F. (1949). Falciparum malaria. In Malariology (ed. BOYD, M. F.), pp. 966–994. Philadelphia, W. B. Saunders.
KNIGHT, J. C., UDALOVA, I., HILL, A. V. S., GREENWOOD, B. M., PESHU, N., MARSH, K. & KWIATKOWSKI, D. (1999). A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nature Genetics 22, 145–150.CrossRefGoogle Scholar
KUN, J. F. J., MORDMULLER, B., LELL, B., LEHMAN, L. G., LUCKNER, D. & KREMSNER, P. G. (1998). Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet 351, 265–266.CrossRefGoogle Scholar
KWIATKOWSKI, D., CANON, J. G., MANOGUE, K. R., CERAMI, A., DINARELLO, C. A. & GREENWOOD, B. M. (1989). Tumor necrosis factor production in falciparum malaria and its association with schizont rupture. Clinical and Experimental Immunology 77, 361–366.Google Scholar
KWIATKOWSKI, D., HILL, A. V. S., SAMBOU, I., TWUMASI, P., CASTRACANE, J., MANOGUE, K. R., CERAMI, A., BREWSTER, D. R. & GREENWOOD, B. M. (1990). TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336, 1201–1204.CrossRefGoogle Scholar
LEHMAN, L. G., PRADA, J. & KREMSNER, P. G. (1998). Protection of mice previously infested with Plasmodium vinckei against subsequent Salmonella enteritidis infection is associated with nitric oxide production capacity. Parasitology Research 84, 63–68.Google Scholar
LIEW, F. Y., MILLOTT, S., PARKINSON, C., PALMER, R. M. & MONCADA, S. (1990). Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. Journal of Immunology 144, 4794–4797.Google Scholar
MACFARLANE, A. S., HUANG, D., SCHWACHA, M. G., MEISSLER, J. J., GAUGHAN, J. P. & EISENSTEIN, T. K. (1998). Nitric oxide mediates immunosuppression induced by Listeria monocytogenes infection: quantitative studies. Microbial Pathogenesis 25, 267–277.CrossRefGoogle Scholar
MACFARLANE, A. S., SCHWACHA, M. G. & EISENSTEIN, T. K. (1999). In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen. Infection and Immunity 67, 891–898.Google Scholar
MAEGRAITH, B. (1948). Pathological Process in Malaria and Blackwater Fever. Oxford, Blackwell.
MAITLAND, K., WILLIAMS, T. N. & NEWBOLD, C. I. (1997). Plasmodium vivax and P. falciparum: biological interactions and the possibility of cross-species immunity. Parasitology Today 13, 227–231.Google Scholar
MARSH, K., ENGLISH, M., CRAWLEY, J. & PESHU, N. (1996). The pathogenesis of severe malaria in African children. Annals of Tropical Medicine and Parasitology 90, 395–402.CrossRefGoogle Scholar
MATSUMOTO, J., KAWAI, S., TERAO, K., KIRINOKI, M., YASUTOMI, Y., AIKAWA, M. & MATSUDA, H. (2000). Malaria infection induces rapid elevation of the soluble fas ligand level in serum and subsequent T lymphocytopenia: Possible factors responsible for the differences in susceptibility of two species of Macaca monkeys to Plasmodium coatneyi infection. Infection and Immunity 68, 1183–1188.CrossRefGoogle Scholar
MATSUMOTO, S., YUKITAKE, H., KANBARA, H. & YAMADA, T. (1998). Recombinant Mycobacterium bovis Bacillus Calmette-Guérin secreting merozoite surface protein 1 (MSP1) induces protection against rodent malaria parasite infection depending on MSP1-stimulated interferon-gamma and parasite-specific antibodies. Journal of Experimental Medicine 188, 845–854.CrossRefGoogle Scholar
MCGUIRE, W., KNIGHT, J. C., HILL, A. V. S., ALLSOPP, C. E. M., GREENWOOD, B. M. & KWIATKOWSKI, D. (1999). Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles. Journal of Infectious Diseases 179, 287–290.CrossRefGoogle Scholar
MEGE, J. L., MAURIN, M., CAPO, C. & RAOULT, D. (1997). Coxiella burnetii: the ‘query’ fever bacterium – a model of immune subversion by a strictly intracellular microorganism. FEMS Microbiology Reviews 19, 209–217.Google Scholar
MELI, R., RASO, G. M., BENTIVOGLIO, C., NUZZO, I., GALDIERO, M. & DI CARLO, R. (1996). Recombinant human prolactin induces protection against Salmonella typhimurium infection in the mouse: role of nitric oxide. Immunopharmacology 34, 1–7.CrossRefGoogle Scholar
NAKANE, A., YAMADA, K., HASEGAWA, S., MIZUKI, D., MIZUKI, M., SASAKI, S. & MIURA, T. (1999). Endogenous cytokines during a lethal infection with Listeria monocytogenes in mice. FEMS Microbiology Letters 175, 133–142.CrossRefGoogle Scholar
NUMATA, M., SUZUKI, S., MIYAZAWA, N., MIYASHITA, A., NAGASHIMA, Y., INOUE, S., KANEKO, T. & OKUBO, T. (1998). Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs. Journal of Immunology 160, 3031–3037.Google Scholar
NYKA, W. (1957). Enhancement of resistance to turberculosis in mice experimentally infected with B. abortus. American Review of Tuberculosis 73, 251–257.Google Scholar
OLD, L. J., CLARKE, D. A. & BENACERRAF, B. (1959). Effect of Bacillus Calmette Guérin infection on transplanted tumours in the mouse. Nature 184, 291–292.CrossRefGoogle Scholar
PRADA, J. & KREMSNER, P. G. (1995). Enhanced production of reactive nitrogen intermediates in human and murine malaria. Parasitology Today 11, 409–410.CrossRefGoogle Scholar
RAZIUDDIN, S., ABDALLA, R. E., EL AWAD, E. H. & ALJANADI, M. (1994). Immunoregulatory and proinflammatory cytokine production in visceral and cutaneous leishmaniasis. Journal of Infectious Diseases 170, 1037–1040.CrossRefGoogle Scholar
ROCKETT, K. A., AWBURN, M. M., COWDEN, W. B. & CLARK, I. A. (1991). Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infection and Immunity 59, 3280–3283.Google Scholar
ROOK, G. A. W., TAVERNE, J., LEVETON, C. & STEELE, J. (1987). The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis. Immunology 62, 229–234.Google Scholar
ROSENBLATTBIN, H., KLEIN, A. & SREDNI, B. (1996). Antibabesial effect of the immunomodulator AS101 in mice: role of increased production of nitric oxide. Parasite Immunology 18, 297–306.CrossRefGoogle Scholar
ROTHE, J., LESSLAUER, W., LOTSCHER, H., LANG, Y., KOEBEL, P., KONTGEN, F., ALTHAGE, A., ZINKERNAGEL, R., STEINMETZ, M. & BLUETHMANN, H. (1993). Mice lacking the tumour necrosis factor receptor-1 are resistant to TNF-Mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 364, 798–802.CrossRefGoogle Scholar
RUETTEN, H., SOUTHAN, G. J., ABATE, A. & THIEMERMANN, C. (1996). Attenuation of endotoxin-induced multiple organ dysfunction by 1-amino-2-hydroxy-guanidine, a potent inhibitor of inducible nitric oxide synthase. British Journal of Pharmacology 118, 261–270.CrossRefGoogle Scholar
SALVIN, S. B., RIBI, E., GRANGER, D. L. & YOUNGNER, J. S. (1975). Migration inhibitory factor and type II interferon in the circulation of mice sensitized with mycobacterial components. Journal of Immunology 114, 354–359.Google Scholar
SCHWARTZ, D., MENDONCA, M., SCHWARTZ I. XIA, Y. Y., SATRIANO, J., WILSON, C. B. & BLANTZ, R. C. (1997). Inhibition of constitutive nitric oxide synthase (NOS) by nitric oxide generated by inducible NOS after lipopolysaccharide administration provokes renal dysfunction in rats. Journal of Clinical Investigation 100, 439–448.CrossRefGoogle Scholar
SHARMA, S. D. & MIDDLEBROOK, G. (1977). Antibacterial product of peritoneal exudate cell cultures from guinea pigs infected with Mycobacteria, Listeriae, and Rickettsiae. Infection and Immunity 15, 745–750.Google Scholar
SMRKOVSKI, L. L. & LARSON, C. L. (1977). Effect of treatment with BCG on the course of visceral leishmaniasis in BALB/c mice. Infection and Immunity 16, 249–257.Google Scholar
SPRIGGS, D. R., SHERMAN, M. L., MICHIE, H., ARTHUR, K. A., IMAMURA, K., WILMORE, D., FREI, E. & KUFE, D. W. (1988). Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase 1 and pharmacologic study. Journal of the National Cancer Institute 80, 1039–1044.Google Scholar
SWARTZBERG, J. E., KRAHENBUHL, J. L. & REMINGTON, J. S. (1975). Dichotomy between macrophage activation and degree of protection against Listeria monocytogenes and Toxoplasma gondii in mice stimulated with Corynebacterium parvum. Infection and Immunity 12, 1037–1043.Google Scholar
TALIAFERRO, W. H. & CANNON, P. R. (1936). The cellular reactions during primary infections and super-infections of Plasmodium brasilianum in Panamanian monkeys. Journal of Infectious Diseases 59, 72–83.CrossRefGoogle Scholar
TAYLOR, T. E., BORGSTEIN, A. & MOLYNEUX, M. E. (1993). Acid-base status in paediatric Plasmodium falciparum malaria. Quarterly Journal of Medicine 86, 99–109.Google Scholar
TITUS, R. G., SHERRY, B. & CERAMI, A. (1989). Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. Journal of Experimental Medicine 170, 2097–2104.CrossRefGoogle Scholar
TOKAREVICH, N. K., PROKOPYEV, A. A., PROKOPYEVA, E. D., SIMBIRTSEV, A. S., TOROPOVA, B. G., DAITER, A. B. & KETLINSKY, S. A. (1992). Role of tumor necrosis factor and interleukin-1 in the formation of resistance in experimental Q fever. Zhurnal Mikrobiologii Epidemiologii I Immunobiologii 5, 46–47.Google Scholar
TRACEY, K. J., BEUTLER, B., LOWRY, S. F., MERRYWEATHER, J., WOLPE, S., MILSARK, I. W., HARIRI, R. J., FAHEY, T. J., ZENTELLA, A., ALBERT, J. D., SHIRES, G. T. & CERAMI, A. (1986). Shock and tissue injury induced by recombinant human cachectin. Science 234, 470–474.CrossRefGoogle Scholar
TRACEY, K. J., FONG, Y., HESSE, D. G., MANOGUE, K. R., LEE, A. T., KUO, G. C., LOWRY, S. F. & CERAMI, A. (1987a). Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal shock bacteraemia. Nature 330, 662–664.Google Scholar
TRACEY, K. J., LOWRY, S. F., FAHEY, T. J., ALBERT, J. D., FONG, Y., HESSE, D., BEUTLER, B., MANOGUE, K. R., CALVANO, S., CERAMI, A. & SHIRES, G. T. (1987b). Cachectin/tumor necrosis factor induces lethal shock and stress hormone response in the dog. Surgery, Gynecology and Obstetrics 164, 415–422.Google Scholar
YOUDIN, S., MOSER, M. & STUTMAN, O. (1974). Non-specific suppression of tumour growth by an immune reaction to Listeria monocytogenes. Journal of the National Cancer Institute 52, 193–198.CrossRefGoogle Scholar
ZHAN, Y. F., LIU, Z. Q. & CHEERS, C. (1996). Tumor necrosis factor alpha and interleukin-12 contribute to resistance to the intracellular bacterium Brucella abortus by different mechanisms. Infection and Immunity 64, 2782–2786.Google Scholar
ZINKERNAGEL, R. M. (1976). Cell-mediated immune response to Salmonella typhimurium infection in mice: development of nonspecific bacteriocidal activity against Listeria monocytogenes. Infection and Immunity 13, 1069–1073.Google Scholar