Regulation and role of IFN-gamma in the innate resistance to infection with Chlamydia pneumoniae

By using mice genomically lacking IFN-gamma R, IL-12, perforin, and recombi nation-activating gene-1 (RAG-1), we analyzed the regulation and importance of IFN-gamma in the control of infection with Chlamydia pneumoniae. IL-12 participates in resistance of mice to C. pneumoniae, probably by regulating the protective levels of IFN-gamma mRNA. In turn, IFN-gamma is necessary f or the increased IL-12p40 mRNA accumulation that occurs in lungs during inf ection with C. pneumoniae, suggesting a positive feedback regulation betwee n these two cytokines. In experiments including RAG-1(-/-)/IFN-gamma R-/- m ice we showed that IFN-gamma produced by innate cells controls the bacteria l load and is necessary for the increased accumulation of transcripts for e nzymes controlling high output NO release (inducible NO synthase), superoxi de production (gp-91 NADPH oxidase), and catalyzis of tryptophan (indoleami ne 2,3-dioxygenase (IDO)), mechanisms probably related to bacterial killing . Adaptive immune reponses diminish the levels of IFN-gamma and IL-12 mRNA and thereby the levels of inducible NO synthase, IDO, and gp91 NADPH oxidas e transcripts, By using RAG-1(-/-)/ perforin(-/-) mice, we excluded the ove rt participation of NK cell cytotoxicity in the control of C. pneumoniae. H owever, NK cells and probably other innate immune cells release IFN-gamma d uring the bacterial infection.