Mice defective in Fas are highly susceptible to Leishmania major infection despite elevated IL-12 synthesis, strong Th1 responses, and enhanced nitric oxide production.
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.
Huang
F P
FP
Department of Immunology, University of Glasgow, Western Infirmary, United Kingdom.
Xu
D
D
Esfandiari
E O
EO
Sands
W
W
Wei
X Q
XQ
Liew
F Y
FY
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*
D019014:fas Receptor; D018664:Interleukin-12; D009569:Nitric Oxide