IL-1β has been implicated in the development of oviduct pathology during Chlamydia muridarum genital
infection in the mouse model. The goal of this study was to characterize the role of
IL-1 signaling and the
inflammasome-activation pathways during genital chlamydial
infection. Compared with control mice, IL-1R-deficient mice displayed delayed clearance and increased chlamydial colonization. Consistent with the role for
IL-1 signaling in
infection clearance, mice deficient for the IL-1R antagonist cleared
infection at a faster rate. Despite increased
infection, IL-1R-deficient mice had significantly reduced oviduct pathology, which was associated with decreased numbers of neutrophils, but more macrophages, in the genital tract. IL-1β secretion is dependent on caspase-1 and apoptosis-associated speck-like
protein containing caspase recruitment domain (ASC)
inflammasome during in vitro
infection of primed macrophages with C. muridarum. To investigate the role of
inflammasome components during in vivo genital
infection, mice lacking NLRP3, NLRC4, and ASC were tested and found to display no reduction in oviduct pathology compared with control mice. Mice deficient for ASC displayed a prolonged course of
infection, which was associated with reduced T cell recruitment and proliferation. Further, ASC-deficient mice displayed normal levels of IL-1β in genital secretions. However, a significant decrease in caspase-1-dependent
IL-18 was observed in both ASC- and NLRP3-deficient mice. These data demonstrate a major role for
IL-1 signaling, but a limited role for the
inflammasome pathway, in IL-1β secretion and development of oviduct pathology during genital chlamydial
infection. The data also suggest an IL-1-independent role for ASC in adaptive immunity during genital chlamydial
infection.