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Role of oxidative stress and apoptosis in the cellular response of murine macrophages upon Leishmania infection

Published online by Cambridge University Press:  10 July 2012

MAARTJE DESCHACHT ,
TIM VAN ASSCHE ,
SARAH HENDRICKX ,
HIDDE BULT ,
LOUIS MAES  and
PAUL COS
MAARTJE DESCHACHT
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
TIM VAN ASSCHE
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
SARAH HENDRICKX
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
HIDDE BULT
Affiliation:
Division of Pharmacology, Faculty of Medicine, University of Antwerp, Wilrijk, Belgium
LOUIS MAES
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
PAUL COS*
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
*
*Corresponding author: Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Universiteitsplein 1, B-2610 Antwerp, Belgium. Tel: +32 3 265 2628. Fax: +32 3 265 2681. E-mail: paul.cos@ua.ac.be
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Summary

Leishmania parasites are able to survive in the macrophage, one of the most hostile environments of the vertebrate host. The present study investigated how Leishmania infection influences these host cell defence mechanisms. Macrophages were infected with antimony-susceptible and -resistant Leishmania strains. Free radical production in Leishmania-infected macrophages was measured by electron paramagnetic resonance. Apoptosis was detected with fluorescence microscopy using Annexin-V FITC labelling and with Western blotting to detect caspase-3 cleavage. Independent of their drug susceptibility profile or species background, all studied Leishmania strains induced a similar increase in free radical production in macrophages. O2●− production was significantly elevated during phagocytosis of the stationary phase promastigotes. Conversely, NO levels increased later in the infection and none of the strains induced capsase-3 cleavage. Leishmania donovani infection led to phosphatidylserine externalization only in RAW 264.7 cells. After an initial burst of O2●− during phagocytosis of promastigotes, amastigotes protect themselves by decreasing the O2●− production to the basal level. An increased NO production was observed 6 h after infection. Finally, induction of cell death is probably not essential in the survival of the parasite within the macrophage.

Keywords

superoxidenitric oxideEPRapoptosisLeishmania infantumLeishmania donovani
Type
Research Article
Information
Parasitology , Volume 139 , Issue 11 , September 2012 , pp. 1429 - 1437
Copyright
Copyright © Cambridge University Press 2012

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References

REFERENCES

Akarid, K., Arnoult, D., Micic-Polianski, J., Sif, J., Estaquier, J. and Ameisen, J. C. (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. 10.1189/jlb.1001877 [doi]; jlb.1001877 [pii]CrossRefGoogle ScholarPubMed
Bogdan, C. and Rollinghoff, M. (1998). The immune response to Leishmania: mechanisms of parasite control and evasion. International Journal for Parasitology 28, 121–134. S0020751997001690 [pii]CrossRefGoogle ScholarPubMed
Burchmore, R. J. and Barrett, M. P. (2001). Life in vacuoles–nutrient acquisition by Leishmania amastigotes. International Journal for Parasitology 31, 1311–1320. S0020-7519(01)00259-4 [pii]CrossRefGoogle ScholarPubMed
Channon, J. Y., Roberts, M. B. and Blackwell, J. M. (1984). A study of the differential respiratory burst activity elicited by promastigotes and amastigotes of Leishmania donovani in murine resident peritoneal macrophages. Immunology 53, 345–355.Google ScholarPubMed
Coelho-Finamore, J. M., Freitas, V. C., Assis, R. R., Melo, M. N., Novozhilova, N., Secundino, N. F., Pimenta, P. F., Turco, S. J. and Soares, R. P. (2011). Leishmania infantum: Lipophosphoglycan intraspecific variation and interaction with vertebrate and invertebrate hosts. International Journal for Parasitology 41, 333–342. S0020-7519(10)00355-3 [pii]; 10.1016/j.ijpara.2010.10.004 [doi]CrossRefGoogle ScholarPubMed
Cunha, F. Q., Assreuy, J., Moncada, S. and Liew, F. Y. (1993). Phagocytosis and induction of nitric oxide synthase in murine macrophages. Immunology 79, 408–411.Google ScholarPubMed
Deschacht, M., Horemans, T., Martinet, W., Bult, H., Maes, L. and Cos, P. (2010). Comparative EPR study of different macrophage types stimulated for superoxide and nitric oxide production. Free Radical Research 44, 763–772. 10.3109/10715761003782288 [doi]CrossRefGoogle ScholarPubMed
Gantt, K. R., Goldman, T. L., McCormick, M. L., Miller, M. A., Jeronimo, S. M., Nascimento, E. T., Britigan, B. E. and Wilson, M. E. (2001). Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi. Journal of Immunology 167, 893–901.CrossRefGoogle ScholarPubMed
Getti, G. T., Cheke, R. A. and Humber, D. P. (2008). Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites/ Parasitology 135, 1391–1399. S0031182008004915 [pii]; 10.1017/S0031182008004915 [doi]CrossRefGoogle Scholar
Green, S. J., Crawford, R. M., Hockmeyer, J. T., Meltzer, M. S. and Nacy, C. A. (1990). Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha. Journal of Immunology 145, 4290–4297.CrossRefGoogle ScholarPubMed
Haidaris, C. G. and Bonventre, P. F. (1982). A role for oxygen-dependent mechanisms in killing of Leishmania donovani tissue forms by activated macrophages. Journal of Immunology 129, 850–855.CrossRefGoogle ScholarPubMed
Haimeur, A., Brochu, C., Genest, P., Papadopoulou, B. and Ouellette, M. (2000). Amplification of the ABC transporter gene PGPA and increased trypanothione levels in potassium antimonyl tartrate (SbIII) resistant Leishmania tarentolae. Molecular and Biochemical Parasitology 108, 131–135. S0166685100001870 [pii]CrossRefGoogle ScholarPubMed
Heussler, V. T., Kuenzi, P. and Rottenberg, S. (2001). Inhibition of apoptosis by intracellular protozoan parasites. International Journal for Parasitology 31, 1166–1176. S0020-7519(01)00271-5 [pii]CrossRefGoogle ScholarPubMed
Kantengwa, S., Muller, I., Louis, J. and Polla, B. S. (1995). Infection of human and murine macrophages with Leishmania major is associated with early parasite heat shock protein synthesis but fails to induce a host cell stress response. Immunology and Cell Biology 73, 73–80. 10.1038/icb.1995.12 [doi]CrossRefGoogle ScholarPubMed
Kumar, P., Pai, K., Pandey, H. P. and Sundar, S. (2002). NADH-oxidase, NADPH-oxidase and myeloperoxidase activity of visceral leishmaniasis patients. Journal of Medical Microbiology 51, 832–836.CrossRefGoogle ScholarPubMed
Kumar, R., Pai, K. and Sundar, S. (2001). Reactive oxygen intermediates, nitrite and IFN-gamma in Indian visceral leishmaniasis. Clinical and Experimental Immunology 124, 262–265. cei1551 [pii]CrossRefGoogle ScholarPubMed
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. Journal of Eukaryotic Microbiology 52, 211–217. JEU05-3368 [pii]; 10.1111/j.1550-7408.2005.00026.x [doi]CrossRefGoogle ScholarPubMed
Lodge, R. and Descoteaux, A. (2006). Phagocytosis of Leishmania donovani amastigotes is Rac1 dependent and occurs in the absence of NADPH oxidase activation. European Journal of Immunology 36, 2735–2744. 10.1002/eji.200636089 [doi]CrossRefGoogle ScholarPubMed
Lodge, R., Diallo, T. O. and Descoteaux, A. (2006). Leishmania donovani lipophosphoglycan blocks NADPH oxidase assembly at the phagosome membrane. Cellular Microbiology 8, 1922–1931. CMI758 [pii]; 10.1111/j.1462-5822.2006.00758.x [doi]CrossRefGoogle ScholarPubMed
Luder, C. G., Gross, U., and Lopes, M. F. (2001). Intracellular protozoan parasites and apoptosis: diverse strategies to modulate parasite-host interactions. Trends in Parasitolgy 17, 480–486. S1471-4922(01)02016-5 [pii]CrossRefGoogle ScholarPubMed
Mandal, G., Wyllie, S., Singh, N., Sundar, S., Fairlamb, A. H. and Chatterjee, M. (2007). Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony. Parasitology 134, 1679–1687. S0031182007003150 [pii]; 10.1017/S0031182007003150 [doi]CrossRefGoogle ScholarPubMed
Moore, K. J. and Matlashewski, G. (1994). Intracellular infection by Leishmania donovani inhibits macrophage apoptosis. Journal of Immunology 152, 2930–2937.CrossRefGoogle ScholarPubMed
Mukhopadhyay, R., Dey, S., Xu, N., Gage, D., Lightbody, J., Ouellette, M. and Rosen, B. P. (1996). Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Proceedings of the National Academy of Sciences, USA 93, 10383–10387.CrossRefGoogle ScholarPubMed
Murray, H. W. (1981). Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages. Journal of Experimental Medicine 153, 1302–1315.CrossRefGoogle ScholarPubMed
Panaro, M. A., Brandonisio, O., Sisto, M., Acquafredda, A., Leogrande, D., Fumarola, L. and Mitolo, V. (2001). Nitric oxide production by Leishmania-infected macrophages and modulation by prostaglandin E2. Clinical and Experimental Medicine 1, 137–143.CrossRefGoogle ScholarPubMed
Panaro, M. A., Lisi, S., Mitolo, V., Acquafredda, A., Fasanella, A., Carelli, M. G. and Brandonisio, O. (1998). Evaluation of killing, superoxide anion and nitric oxide production by Leishmania infantum-infected dog monocytes. Cytobios 95, 151–160.Google ScholarPubMed
Pham, N. K., Mouriz, J., and Kima, P. E. (2005). Leishmania pifanoi amastigotes avoid macrophage production of superoxide by inducing heme degradation. Infection and Immunity 73, 8322–8333. 73/12/8322 [pii]; 10.1128/IAI.73.12.8322-8333.2005 [doi]CrossRefGoogle ScholarPubMed
Proudfoot, L., Nikolaev, A. V., Feng, G. J., Wei, W. Q., Ferguson, M. A., Brimacombe, J. S. and Liew, F. Y. (1996). Regulation of the expression of nitric oxide synthase and leishmanicidal activity by glycoconjugates of Leishmania lipophosphoglycan in murine macrophages. Proceedings of the National Academy of Sciences, USA 93, 10984–10989.CrossRefGoogle ScholarPubMed
Proudfoot, L., Schneider, P., Ferguson, M. A. and McConville, M. J. (1995). Biosynthesis of the glycolipid anchor of lipophosphoglycan and the structurally related glycoinositolphospholipids from Leishmania major. The Biochemical Journal 308, 45–55.CrossRefGoogle ScholarPubMed
Ruhland, A., Leal, N. and Kima, P. E. (2007). Leishmania promastigotes activate PI3 K/Akt signalling to confer host cell resistance to apoptosis. Cellular Microbiology 9, 84–96. CMI769 [pii]; 10.1111/j.1462-5822.2006.00769.x [doi]CrossRefGoogle Scholar
Shweash, M., Adrienne, M. H., Schroeder, J., Neamatallah, T., Bryant, C. E., Millington, O., Mottram, J. C., Alexander, J. and Plevin, R. (2011). Leishmania mexicana promastigotes inhibit macrophage IL-12 production via TLR-4 dependent COX-2, iNOS and arginase-1 expression. Molecular Immunology 48, 1800–1808. S0161-5890(11)00165-9 [pii]; 10.1016/j.molimm.2011.05.013 [doi]CrossRefGoogle ScholarPubMed
Van Assche, T., Deschacht, M., Inocêncio da Luz, R., Maes, L. and Cos, P. (2011). Leishmania-macrophage interactions: insights into the redox biology. Free Radical Biology and Medicine 51, 337–351. S0891-5849(11)00313-3 [pii]; 10.1016/j.freeradbiomed.2011.05.011 [doi]CrossRefGoogle ScholarPubMed
Vray, B. (2002). Macrophages in parasitic infection. In The Macrophage (ed. Burke, B. and Lewis, C.), pp. 255–304. Oxford University Press, Oxford, UK.Google Scholar
Wang, X., Zhao, Q., Matta, R., Meng, X., Liu, X., Liu, C. G., Nelin, L. D. and Liu, Y. (2009). Inducible nitric-oxide synthase expression is regulated by mitogen-activated protein kinase phosphatase-1. Journal of Biological Chemistry 284, 27123–27134. M109.051235 [pii]; 10.1074/jbc.M109.051235 [doi]CrossRefGoogle ScholarPubMed
Wilkins-Rodriguez, A. A., Escalona-Montano, A. R., Aguirre-Garcia, M., Becker, I. and Gutierrez-Kobeh, L. (2010). Regulation of the expression of nitric oxide synthase by Leishmania mexicana amastigotes in murine dendritic cells. Experimental Parasitology 126, 426–434. S0014-4894(10)00258-4 [pii]; 10.1016/j.exppara.2010.07.014 [doi]CrossRefGoogle ScholarPubMed
Wilson, M. E., Andersen, K. A. and Britigan, B. E. (1994). Response of Leishmania chagasi promastigotes to oxidant stress. Infection and Immunity 62, 5133–5141.CrossRefGoogle ScholarPubMed
Wyllie, S., Mandal, G., Singh, N., Sundar, S., Fairlamb, A. H. and Chatterjee, M. (2010). Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates. Molecular and Biochemical Parasitology 173, 162–164. S0166-6851(10)00138-6 [pii]; 10.1016/j.molbiopara.2010.05.015 [doi]CrossRefGoogle ScholarPubMed
Wyllie, S., Vickers, T. J. and Fairlamb, A. H. (2008). Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials. Antimicrobial Agents and Chemotherapy 52, 1359–1365. AAC.01563-07 [pii]; 10.1128/AAC.01563-07 [doi]CrossRefGoogle ScholarPubMed