Roles of Interleukin-12 and Gamma Interferon in MurineChlamydia pneumoniaeInfection

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Abstract
BALB/c and strain 129 mice infected intranasally withChlamydia pneumoniaedisplayed a moderate-to-severe inflammation in the lungs and produced interleukin-12 (IL-12), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-10, with peak levels on days 1 to 3 postinfection (p.i.), returning to basal levels by day 16 p.i. Anti-IL-12 treatment resulted in less-severe pathological changes but higher bacterial titers on days 3 and 7 p.i. By day 16 p.i., the inflammatory responses of control antibody-treated mice subsided. The bacterial titers of both anti-IL-12- and control antibody-treated mice decreased within 3 weeks to marginally detectable levels. Anti-IL-12 treatment significantly reduced lung IFN-γ production and in vitro spleen cell IFN-γ production in response to eitherC. pneumoniaeor concanavalin A. In γ-irradiated infected mice, cytokine production was delayed, and this delay correlated with high bacterial titers in the lungs. FollowingC. pneumoniaeinfection, 129 mice lacking the IFN-γ receptor α chain gene (G129 mice) produced similar IL-12 levels and exhibited similarly severe pathological changes but had higher bacterial titers than 129 mice. However, by day 45 p.i., bacterial titers became undetectable in both wild-type 129 and G129 mice. Thus, duringC. pneumoniaelung infection, IL-12, more than IFN-γ, plays a role in pulmonary-cell infiltration. IFN-γ and IL-12, acting mostly through its induction of IFN-γ and Th1 responses, play an important role in controlling acuteC. pneumoniaeinfection in the lungs, but eventually all mice control the infection to undetectable levels by IL-12- and IFN-γ-independent mechanisms.