Clearance ofChlamydia trachomatisfrom the Murine Genital Mucosa Does Not Require Perforin-Mediated Cytolysis or Fas-Mediated Apoptosis

Abstract

The molecular mechanisms of resistance to genital infection with the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis are unknown. A role for major histocompatibility complex class II-restricted, interleukin-12-dependent CD4+T cells has been established, but the functional activity of these cells does not depend on secretion of gamma interferon. Here we examined the potential contribution of T-cell-mediated cytotoxicity and apoptosis to mucosal clearance of MoPn by using mice deficient in the molecular mediators of target cell lysis. Animals lacking perforin, Fas, Fas ligand, or both perforin and Fas ligand were infected genitally with C. trachomatis MoPn and monitored for expression of immunity to chlamydial antigens and clearance of MoPn from the genital mucosa. In each case, the profile of spleen cytokine production, the magnitude of the host antibody response, and the kinetics of chlamydial clearance were similar to those of genetically intact controls. Compensatory overproduction of tumor necrosis factor alpha, an alternate mediator of apoptosis in certain cell types, did not appear to account for the ability of mutant mice to resolveChlamydia infections. These results fail to support CD4+ T-cell-mediated apoptosis or CD8+T-cell-mediated cytotoxicity as being critical to the clearance ofC. trachomatis MoPn urogenital infections.

Degradation of Transcription Factor Rfx5 during the Inhibition of Both Constitutive and Interferon γ–Inducible Major Histocompatibility Complex Class I Expression in Chlamydia-Infected Cells

“…Therefore, the chlamydial suppression of MHC class I expression, occurring at a time when host T cell attack on the chlamydia-infected cells is most likely to happen, may be beneficial for chlamydial survival in the infected hosts. This hypothesis is further supported by various previous findings that mice deficient in β2M 48 or perforin 49 did not show enhanced susceptibility to chlamydial infection.…”

Views of immunology: effector T cells

“…Similarly, in a mouse model of Chlamydia pneumoniae primary infection, CD8 + T-cell protection was dependent on IFN-c, but independent of perforin (16). Moreover, in a mouse model of genital infection with Chlamydia trachomatis, mice deficient in perforin cleared infection equivalently to wildtype mice (17).…”

“…CD8 + T-cell FASL expression is dispensable for protection from hepatic stage infection with either P. berghei and P. yoelii (18). In a mouse model of genital infection with C. trachomatis, mice deficient in FAS or FASL cleared infection equivalently to wildtype mice (17).…”

Perforin and lymphohistiocytic proliferative disorders

“…Perforin‐deficient mice showed increased mortality during chronic infection with Toxoplasma gondii (Denkers et al , 1997) or Histoplasma capsulatum (Zhou et al , 2001). In contrast, perforin‐deficient mice show no delay in clearance of Chlamydia trachomatis (Perry et al , 1999) or Chlamydia pneumonia (Rottenberg et al , 1999).…”