Martins G A, Petkova S B, MacHado F S, Kitsis R N, Weiss L M, Wittner M, Tanowitz H B, Silva J S
Department of Immunology, School of Medicine of Ribeirão Preto-USP, Ribeirão Preto, São Paulo, Brazil.
Immunology. 2001 May;103(1):122-9. doi: 10.1046/j.1365-2567.2001.01216.x.
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.
在小鼠急性克氏锥虫感染期间，许多白细胞会发生凋亡。尽管凋亡被认为与一氧化氮（NO）水平升高和Fas-FasL相互作用有关，但这种现象在调节宿主对克氏锥虫的反应中的重要性尚不清楚。在此，使用Fas表达缺陷小鼠（MRL/MpJ-Fas lpr）和诱导型一氧化氮合酶（iNOS）基因敲除小鼠（iNOS-/-）评估了NO和Fas-FasL诱导的凋亡在调节对克氏锥虫免疫反应中的作用。结果表明，除了感染后减少凋亡诱导外，Fas-FasL相互作用的受损还导致NO产生减少，这是辅助性T细胞2（Th2）细胞因子产生增强的结果。不同的是，阻断NO诱导的凋亡导致细胞因子产生不受控制，而不是偏向Th2细胞因子模式。总之，这些结果表明，Fas和FasL诱导的凋亡可能通过在感染急性期干扰细胞因子和NO的产生而参与调节对克氏锥虫的免疫反应。
