title: Mice defective in Fas are highly susceptible to Leishmania major infection despite elevated IL-12 synthesis, strong Th1 responses, and enhanced nitric oxide production.
abstract: MRL/MP-lpr/lpr (MRL/lpr) mice have a single mutation (lpr) of the fas apoptosis gene. The mutant mice developed significantly smaller lesions than the wild-type mice at the earlier stage of infection with the intracellular protozoan parasite Leishmania major. However, while all the wild-type mice achieved complete lesion resolution, the disease in the mutant mice progressed inexorably. The mutant mice had more IL-12 and nitrite/nitrate in the serum than wild-type mice following infection. Lymphoid cells from infected MRL/lpr mice produced more IFN-gamma but less IL-4 and IL-5 than cells from MRL-+/+ mice. Peritoneal macrophages from the mutant mice also produced more IL-12 and NO after stimulation with LPS. Thus, Fas expression is essential for resistance against leishmaniasis, and Fas-mediated apoptosis may form an integral part of the Th1-mediated microbicidal function.
authors.affiliation: Department of Immunology, University of Glasgow, Western Infirmary, United Kingdom.
authors.forename: F P
authors.initials: FP
authors.lastname: Huang
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: E O
authors.initials: EO
authors.lastname: Esfandiari
authors.forename: W
authors.initials: W
authors.lastname: Sands
authors.forename: X Q
authors.initials: XQ
authors.lastname: Wei
authors.forename: F Y
authors.initials: FY
authors.lastname: Liew
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009569:Nitric Oxide / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology*
chemical_list: D019014:fas Receptor; D018664:Interleukin-12; D009569:Nitric Oxide