Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-20T04:19:35.617Z Has data issue: false hasContentIssue false
  • English
  • Français

Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites?

Published online by Cambridge University Press:  08 September 2008

G. T. GETTI ,
R. A. CHEKE  and
D. P. HUMBER
G. T. GETTI*
Affiliation:
School of Health and Bioscience, University of East London, Stratford Campus, Romford Road, London E15 4LZ, UK Natural Resources Institute, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK
R. A. CHEKE
Affiliation:
Natural Resources Institute, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK
D. P. HUMBER
Affiliation:
School of Health and Bioscience, University of East London, Stratford Campus, Romford Road, London E15 4LZ, UK
*
*Corresponding author: School of Health and Bioscience, University of East London, Stratford Campus, Romford Road, London E15 4LZ, UK. Tel: 020 82237305. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Leishmania parasites invade host macrophages, causing infections that are either limited to skin or spread to internal organs. In this study, 3 species causing cutaneous leishmaniasis, L. major, L. aethiopica and L. tropica, were tested for their ability to interfere with apoptosis in host macrophages in 2 different lines of human monocyte-derived macrophages (cell lines THP-1 and U937) and the results confirmed in peripheral blood mononuclear cells (PBMC). All 3 species induced early apoptosis 48 h after infection (expression of phosphatidyl serine on the outer membrane). There were significant increases in the percentage of apoptotic cells both for U937 and PBMC following infection with each of the 3 species. Early apoptotic events were confirmed by mitochondrial membrane permeabilization detection and caspase activation 48 and 72 h after infection. Moreover, the percentage of infected THP-1 and U937 macrophages increased significantly (up to 100%) following treatment with an apoptosis inducer. Since phosphatidyl serine externalization on apoptosing cells acts as a signal for engulfment by macrophages, induction of apoptosis in the parasitized cells could actively participate in spreading the infection. In summary, parasite-containing apoptotic bodies with intact membranes could be released and phagocytosed by uninfected macrophages.

Keywords

LeishmaniaTHP-1U937infectionapoptosis
Type
Original Articles
Information
Parasitology , Volume 135 , Issue 12 , October 2008 , pp. 1391 - 1399
Copyright
Copyright © 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abu-Zant, A., Santic, M., Molmeret, M., Jones, S., Helbig, J. and Abu Kwaik, Y. (2005). Incomplete activation of macrophage apoptosis during intracellular replication of Legionella pneumophila. Infection and Immunity 73, 5339–5349.CrossRefGoogle ScholarPubMed
Ahr, B., Robert-Hebmann, V., Devaux, C. and Biard-Piechaczyk, M. (2004). Apoptosis of uninfected cells induced by HIV envelope glycoproteins. Retrovirology 1, 12.CrossRefGoogle ScholarPubMed
Akarid, K., Arnoult, D., Micic-Polianski, J., Sif, J., Estaquier, J. and Ameisen, J. (2004). Leishmania major-mediated prevention of programmed cell death induction in infected macrophages is associated with the repression of mitochondrial release of cytochrome c. Journal of Leukocyte Biology 76, 95–103.CrossRefGoogle ScholarPubMed
Belkaid, Y., Mendez, S., Lira, R., Kadambi, N., Milon, G. and Sacks, D. (2000). A natural model of Leishmania major infection reveals a prolonged “silent” phase of parasite amplification in the skin before the onset of lesion formation and immunity. The Journal of Immunology 165, 969–977.CrossRefGoogle ScholarPubMed
Braithwaite, A. W. and Russell, I. A. (2001). Induction of cell death by adenoviruses. Apoptosis 6, 359–370.CrossRefGoogle ScholarPubMed
Chang, K. P. and McGwire, B. S. (2002). Molecular determinants and regulation of Leishmania virulence. Kinetoplastid Biology and Disease 1, 1.CrossRefGoogle ScholarPubMed
Chang, K. P., Reed, S. G., McGwire, B. S. and Soong, L. (2003). Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity. Acta Tropica 85, 375–390.CrossRefGoogle ScholarPubMed
Chen, L. M., Kaniga, K. and Galan, J. E. (1996). Salmonella spp. are cytotoxic for cultured macrophages. Molecular Microbiology 21, 1101–1115.CrossRefGoogle ScholarPubMed
Cocco, R. E. and Ucker, D. S. (2001). Distinct modes of macrophage recognition for apoptotic and necrotic cells are not specified exclusively by phosphatidylserine exposure. Molecular Biology of the Cell 12, 919–930.CrossRefGoogle Scholar
Cosenza, M. A., Zhao, M. L. and Lee, S. C. (2004). HIV-1 expression protects macrophages and microglia from apoptotic death. Neuropathology and Applied Neurobiology 30, 478–490.CrossRefGoogle ScholarPubMed
Daleke, D. L. (2003). Regulation of transbilayer plasma membrane phospholipid asymmetry. Journal of Lipid Research 44, 233–242.CrossRefGoogle ScholarPubMed
Darzynkiewicz, Z., Bruno, S., Del Bino, G., Gorczyca, W., Hotz, M. A., Lassota, P. and Traganos, F. (1992). Features of apoptotic cells measured by flow cytometry. Cytometry 13, 795–808.CrossRefGoogle ScholarPubMed
Davis, J. M. (2002). Cell Culture, a Practical Approach, 2nd Edn. Oxford University Press, Oxford, UK.Google Scholar
de Almeida, M. C., Vilhena, V., Barral, A. and Barral-Netto, M. (2003). Leishmanial infection: analysis of its first steps. A review. Memórias do Instituto Oswaldo Cruz 98, 861–870.CrossRefGoogle ScholarPubMed
Durrbaum-Landmann, I., Gercken, J., Flad, H. D. and Ernst, M. (1996). Effect of in vitro infection of human monocytes with low numbers of Mycobacterium tuberculosis bacteria on monocyte apoptosis. Infection and Immunity 64, 5384–5389.CrossRefGoogle ScholarPubMed
Gebre-Hiwot, A., Tadesse, G., Croft, S. L. and Frommel, D. (1992). An in vitro model for screening antileishmanial drugs: the human leukaemia monocyte cell line, THP-1. Acta Tropica 51, 237–245.CrossRefGoogle Scholar
Gregory, D. J. and Olivier, M. (2005). Subversion of host cell signalling by the protozoan parasite Leishmania. Parasitology 130, 27–35.CrossRefGoogle ScholarPubMed
Grimsley, C. and Ravichandran, K. S. (2003). Cues for apoptotic cell engulfment: eat-me, don't eat-me and come-get-me signals. Trends in Cell Biology 13, 648–656.CrossRefGoogle ScholarPubMed
Hersh, D., Monack, D.M., Smith, M. R., Ghori, N., Falkow, S. and Zychlinsky, A. (1999). The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proceedings of the National Academy of Sciences, USA 96, 2396–2401.CrossRefGoogle ScholarPubMed
Lauber, K., Bohn, E., Krober, S. M., Xiao, Y. J., Blumenthal, S. G., Lindemann, R. K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., Xu, Y., Autenrieth, I. B., Schulze-Osthoff, K., Belka, C., Stuhler, G. and Wesselborg, S. (2003). Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113, 717–730.CrossRefGoogle ScholarPubMed
Lillie, R. D. (1977). H.J. Conn's Biological Stains, 9th Edn. Williams & Wilkins, Baltimore, MD, USA.Google Scholar
Lisi, S., Sisto, M., Acquafredda, A., Spinelli, R., Schiavone, M., Mitolo, V., Brandonisio, O. and Panaro, M. (2005). Infection with Leishmania infantum Inhibits actinomycin D-induced apoptosis of human monocytic cell line U-937. The Journal of Eukaryotic Microbiology 52, 211–217.CrossRefGoogle ScholarPubMed
Monack, D. M., Raupach, B., Hromockyj, A. E. and Falkow, S. (1996). Salmonella typhimurium invasion induces apoptosis in infected macrophages. Proceedings of the National Academy of Sciences, USA 93, 9833–9838.CrossRefGoogle ScholarPubMed
Moore, K. J. and Matlashewski, G. (1994). Intracellular infection by Leishmania donovani inhibits macrophage apoptosis. The Journal of Immunology 152, 2930–2937.CrossRefGoogle ScholarPubMed
Nagata, S. (2000). Apoptotic DNA fragmentation. Experimental Cell Research 256, 12–18.CrossRefGoogle ScholarPubMed
Nakajima-Shimada, J., Zou, C., Takagi, M., Umeda, M., Nara, T. and Aoki, T. (2000). Inhibition of Fas-mediated apoptosis by Trypanosoma cruzi infection. Biochimica et Biophysica Acta 1475, 175–183.CrossRefGoogle ScholarPubMed
Nash, P. B., Purner, M. B., Leon, R. P., Clarke, P., Duke, R. C. and Curiel, T. J. (1998). Toxoplasma gondii-infected cells are resistant to multiple inducers of apoptosis. The Journal of Immunology 160, 1824–1830.CrossRefGoogle ScholarPubMed
Nonaka, T., Kuwabara, T., Mimuro, H., Kuwae, A. and Imajoh-Ohmi, S. (2003). Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages. Microbiology 149, 2513–2527.CrossRefGoogle ScholarPubMed
Ogunkolade, B. W., Colomb-Valet, I., Monjour, L., Rhodes-Feuillette, A., Abita, J. P. and Frommel, D. (1990). Interactions between the human monocytic leukaemia THP-1 cell line and Old and New World species of Leishmania. Acta Tropica 47, 171–176.CrossRefGoogle ScholarPubMed
Pignata, C., Fiore, M., De Filippo, S., Cavalcanti, M., Gaetaniello, L. and Scotese, I. (1998). Apoptosis as a mechanism of peripheral blood mononuclear cell death after measles and varicella-zoster virus infections in children. Pediatric Research 43, 77–83.CrossRefGoogle ScholarPubMed
Rogers, M. E., Ilg, T., Nikolaev, A. V., Ferguson, M. A. and Bates, P. A. (2004). Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature, London 430, 463–467.CrossRefGoogle ScholarPubMed
Ruckdeschel, K., Roggenkamp, A., Lafont, V., Mangeat, P., Heesemann, J. and Rouot, B. (1997). Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis. Infection and Immunity 65, 4813–4821.CrossRefGoogle ScholarPubMed
Sakai, T., Hisaeda, H., Ishikawa, H., Maekawa, Y., Zhang, M., Nakao, Y., Takeuchi, T., Matsumoto, K., Good, R. A. and Himeno, K. (1999). Expression and role of heat-shock protein 65 (HSP65) in macrophages during Trypanosoma cruzi infection: involvement of HSP65 in prevention of apoptosis of macrophages. Microbes and Infection 1, 419–427.CrossRefGoogle ScholarPubMed
Savill, J. (1997). Apoptosis in resolution of inflammation. Journal of Leukocyte Biology 61, 375–380.CrossRefGoogle ScholarPubMed
Savill, J., Fadok, V., Henson, P. and Haslett, C. (1993). Phagocyte recognition of cells undergoing apoptosis. Immunology Today 14, 131–136.CrossRefGoogle ScholarPubMed
Savill, J., Gregory, C. and Haslett, C. (2003). Cell biology. Eat me or die. Science 308, 1516–1517.CrossRefGoogle Scholar
Toure-Balde, A., Sarthou, J. L., Aribot, G., Michel, P., Trape, J. F., Rogier, C. and Roussilhon, C. (1996). Plasmodium falciparum induces apoptosis in human mononuclear cells. Infection and Immunity 64, 744–750.CrossRefGoogle ScholarPubMed
World Health Organization (2004). Report on leishmaniasis. World Health Organization Scientific Working Group on Leishmaniasis.Google Scholar
Zhang, Y., Zhang, Q. H., Wu, L. J., Tashiro, S., Onodera, S. and Ikejima, T. (2004). Atypical apoptosis in L929 cells induced by evodiamine isolated from Evodia rutaecarpa. The Journal of Asian Natural Products Research 6, 19–27.CrossRefGoogle ScholarPubMed