Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice

Infection with Chlamydia pneumoniae is a common cause of acute respiratory disease in man and is also associated with atherosclerotic cardiovascular d isorder. Herein, we have compared bacterial load and immune parameters of C . pneumoniae-infected mice genomically lacking T cell coreceptors, cytokine receptors, or cytotoxic effector molecules. A protective role for CD8(+) c ells is shown by the enhanced severity of infection of CD8(-/-) or TAP-1(-/ -)/beta(2)-microglobulin(-/-) mice. CD8(+) cells hindered a parasite growth -promoting role of CD4(+) T cells, as indicated by the higher sensitivity t o early infection of CD8(-/-) than CD4(-/-)/CD8(-/-) mice, which was furthe r confirmed in experiments in which SCID mice were reconstituted with eithe r CD4(+) or CD4(+) plus CD8(+) T cells. Interestingly, CD4(+) T cells playe d a dual role, detrimental early (14 and 24 days) after infection but prote ctive at later time points (60 days after infection). The CD8(+) T cell pro tection was perforin independent. The early deleterious role of CD4(+) in t he absence of CD8(+) T cells was associated with enhanced IL-4 and IL-10 mR NA levels and delayed IFN-gamma mRNA accumulation in lungs. In line with th is, IFN-gamma R-/- (but not TNFRp55(-/-)) mice showed dramatically increase d susceptibility to C. pneumoniae, linked to reduced inducible nitric oxide synthase (iNOS) mRNA accumulation, but not to diminished levels of specifi c Abs, The increased susceptibility of iNOS(-/-) mice indicates a protectiv e role for iNOS activity during infection with C. pneumoniae, The higher se nsitivity of IFN-gamma R-/- mice to C, pneumoniae compared with that of SCI D or recombination-activating gene-1(-/-) mice suggested a relevant protect ive role of IFN-gamma-dependent innate mechanisms of protection.