title: Elimination of P. berghei liver stages is independent of Fas (CD95/Apo-I) or perforin-mediated cytotoxicity.
abstract: Immunization of mammals with irradiated malaria sporozoites protects from a subsequent contact with the parasite. Protective immunity is directed against the pre-erythrocytic stages of the parasite, sporozoites and liver stages. Specific antibodies neutralize part of the infectious sporozoites infected by the mosquito vector, while liver stages are the target of a cellular immune response which is mediated by T cells. In this study, we evaluated the T-cell dependent protection induced by the infection of P. berghei irradiated sporozoites and the contribution of perforin and of the receptor/ligand system CD95/CD95L, two T cell-dependent mechanisms known to mediate elimination of target cells. Wild type, perforin deficient, CD95 mutant, CD95L mutant and perforin deficient/CD95L mutant mice were immunized with P. berghei irradiated sporozoites and submitted to a challenge with infectious sporozoites. All mice immunized with P. berghei irradiated sporozoites were protected against a sporozoite challenge, including perforin deficient/CD95L mutant animals. These results indicate that T cells do not kill malaria-infected hepatocytes via one of the known pathways, but rather that activated parasite-specific T cells produce cytokines which activate in cascade other mechanisms responsible for the intracellular elimination of the parasite.
authors.affiliation: University of Lausanne, Institute of Biochemistry, Epalinges, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Renggli
authors.forename: M
authors.initials: M
authors.lastname: Hahne
authors.forename: H
authors.initials: H
authors.lastname: Matile
authors.forename: B
authors.initials: B
authors.lastname: Betschart
authors.forename: J
authors.initials: J
authors.lastname: Tschopp
authors.forename: G
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D007114:Immunization; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019014:fas Receptor / Q000235:genetics
chemical_list: D017780:Malaria Vaccines; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin