Fas-FasL interaction modulates nitric oxide production in Trypanosoma cruzi-infected mice.
During acute Trypanosoma cruzi infection in mice, many leucocytes undergo apoptosis. Although apoptosis has been ascribed to increased levels of nitric oxide (NO) and Fas-FasL interaction, the importance of this phenomenon in modulating the host response against T. cruzi is unknown. Herein, the role of NO- and Fas-FasL-induced apoptosis in modulating the immune response to T. cruzi was evaluated using mice deficient in Fas expression (MRL/MpJ-Fas lpr) and inducible nitric oxide synthase (iNOS) knockout mice (iNOS-/-). The results showed that besides decreasing apoptosis induction after infection, impairment of the Fas-FasL interaction resulted in decreased NO production, as a consequence of enhanced T helper 2 (Th2) cytokine production. Differently, blockage of NO-induced apoptosis resulted in uncontrolled cytokine production, rather than a biased Th2 cytokine pattern. Together, these results suggested that Fas and FasL-induced apoptosis could be implied in modulation of the immune response against T. cruzi by interfering with cytokine and NO production during the acute phase of the infection.
Martins
G A
GA
Department of Immunology, School of Medicine of Ribeirão Preto-USP, Ribeirão Preto, São Paulo, Brazil.
Petkova
S B
SB
MacHado
F S
FS
Kitsis
R N
RN
Weiss
L M
LM
Wittner
M
M
Tanowitz
H B
HB
Silva
J S
JS
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018929:Cell Culture Techniques; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D019014:fas Receptor / Q000378:metabolism*
D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D009569:Nitric Oxide