Abstract
We examined the susceptibility of murine Fas-deficient mutants to malaria infection in order to investigate the role of Fas in an experimental murine model of cerebral malaria (CM). We infected mice of B6 and CBA wild-type and mutant backgrounds with Plasmodium berghei ANKA. The incidence of CM in the mutant mice (B6-lpr, CBA-lprcg) was decreased by about 50% compared with wild-type control strains at 2 weeks after infection. We did not observe significant differences of parasitemia during a murine malaria infection with nonlethal Plasmodium yoelii 17XNL between wild-type and lymphoproliferative (lpr) mutant mice of C3H and MRL genetic backgrounds, although B6-lpr mice exhibited significantly higher parasitemia than did B6 mice 12 to 18 days after infection. These results suggest Fas has a possible role in CM but may not play a major role in the proliferation or exclusion of a murine malaria parasite in a nonlethal infection.
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References
Bagot S, Campino S, Penha-Goncalves C, Pied S, Cazennave P, Holmberg D (2002) Identification of two cerebral malaria resistat loci using an inbred wild-derived mouse strain. Proc Natl Acad Sci U S A 99:9919–9923
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. Infect Immun 68:1485–1490
Hu MS, Schwarzman JD, Yeaman GR, Collins J, Seguin R, Khan IA, Kasper LH (1999) Fas-FasL interaction involved in pathogenesis of ocular toxoplasmosis in mice. Infect Immun 67:928–935
Huang FP, Xu D, Esfandiari E, Sands W, Wei X, Liew FL (1998) Mice defective in Fas are highly susceptible to Leishmania major infection despite elevated IL-12 synthesis, strong Th1 responses, and enhanced nitric oxide production. J Immunol 160:4143–4147
Kern P, Dietrich M, Hemmer C, Wellinghausen N (2000) Increased levels of soluble Fas ligand in serum in Plasmodium falciparum malaria. Infect Immun 68:3061–3063
Kimura M, Matsuzawa A (1994) Autoimmunity in mice bearing lprcg: a novel mutant gene. Int Rev Immunol 11:193–210
Langhorne J, Quin SJ, Sanni LA (2002) Mouse models of blood-stage malaria infections: immune responses and cytokines involved in protection and pathology. Chem Immunol 80:204–228
Li C, Seixas E, Langhorne J (2001) Rodent malarias: the mouse as a model for understanding immune responses and pathology induced by the erythrocytic stages of the parasite. Med Microbiol Immunol 189:115–126
Lou J, Lucas R, Grau GE (2001) Pathogenesis of cerebral malaria: recent experimental data and possible applications for humans. Clin Microbiol Rev 14:810–820
Lucas R, Juillard P, Decoster E, Redard M, Burger D, Donati Y, Giroud C, Monso-Hinard C, Kesel TD, Buurman WA, Moore MW, Dayer J, Fiers W, Bluethmann H, Grau GE (1997) Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in experimental cerebral malaria. Eur J Immunol 27:1719–1725
Martins GA, Petkova SB, Machado FS, Kitsis RN, Weiss LM, Wittner M, Tanowitz HB, Silva JS (2001) Fas-FasL interaction modulates nitric oxide production in Trypanosoma cruzi-infected mice. Immunology 103:122–129
Matsumoto J, Kawai S, Terao K, Kirinoki M, Yasutomo 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. Infect Immun 68:1183–1188
Moss JE, Aliprantis AO, Zychlinsky A (1999) The regulation of apoptosis by microbial pathogens. Int Rev Cytol 187:203–259
Nadeau JH (2003) Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13:290–295
Nagata S, Golstein P (1995) The Fas death factor. Science 267:1449–1456
Piguet PF, Kan CD, Vesin C, Rochat A, Donati Y, Barazzone C (2001) Role of CD40-CD40L in mouse severe malaria. Am J Pathol 159:733–742
Piguet PF, Kan CD, Vesin C (2002) Role of tumor necrosis factor receptor 2 (TNFR2) in cerebral malaria in mice. Lab Invest 82:1155–1166
Pino P, Vouldoukis I, Kolb JP, Mahmoudi N, Desportes-Livage I, Bricaire F, Danis M, Dugas B, Mazier D (2000) Plasmodium falciparum-infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis 187:1283–1290
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Ohno, T., Kobayashi, F. & Nishimura, M. Fas has a role in cerebral malaria, but not in proliferation or exclusion of the murine parasite in mice. Immunogenetics 57, 293–296 (2005). https://doi.org/10.1007/s00251-005-0791-5
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DOI: https://doi.org/10.1007/s00251-005-0791-5