Genetically determined differences in IL-10 and IFN-gamma responses correlate with clearance of Chlamydia trachomatis mouse pneumonitis infection

Abstract

Cytokine patterns elicited by infection are critical in the regulation of the adaptive immune response and in the resolution of infection. Using a murine model of pneumonia induced by intranasal inoculation with the Chlamydia trachomatis mouse pneumonitis (MoPn) biovar, we found that the patterns of immune responses and cytokine production by spleen cells were correlated with quantitative growth of MoPn in the lungs of C57BL/6 and BALB/c mice. Specifically, BALB/c (H-2d) mice had a significantly higher mortality rate and a slower clearance of the organism from the lungs than did C57BL/6 mice (H-2b). BALB/c mice exhibited higher IL-10 production, higher IgG1 Ab responses, and less IFN-gamma production than C57BL/6 mice, which showed higher IFN-gamma production, stronger delayed-type hypersensitivity (DTH) responses, and significantly less IL-10 production. In vivo neutralization of IL-10 in BALB/c mice with an anti-IL-10 mAB during MoPn infection significantly increased the DTH response and enhanced clearance of MoPn. These findings support the hypothesis that excessive IL-10 production in BALB/c mice inhibits Th1-like responses, including IFN-gamma expression and the DTH response following chlamydial infection and consequently delay infection resolution.