The major contribution of IL-1 alpha and caspase-11 in oviduct pathology during Chlamydia infection in the mouse model

Abstract

Abstract The mouse model of genital Chlamydia trachomatis infection simulates the human chlamydial disease resulting in oviduct damage leading to hydrosalpinx. Using this model, we have shown that signaling by IL-1R is a major contributor of oviduct disease during infection. In the current study, we have investigated the specific contribution of IL-1 alpha and IL-1 beta that signal thorough IL-1R. Further, the contribution of caspase11-mediated cell-death that results in the release of IL-1 alpha and IL-1 beta were investigated. IL-1 alpha KO mice developed significantly less incidence (5%) of hydrosalpinx compared to WT mice (75%) (p=<0.001) upon infection. IL-1 beta KO mice had a reduced incidence in hydrosalpinx than WT mice, but significantly higher than IL-1 alpha KO mice. To determine the mechanism of IL-1 alpha release, infection course and pathology in caspase-1-11 KO mice and caspase-11 KO mice were determined. Both caspase-11 and caspase-1-11 KO mice displayed a reduced incidence of hydrosalpinx. Since the caspase-1 adaptor, ASC KO mice do not show a reduced incidence in pathology, our data suggest that caspase-11 activation is sufficient to drive the pathology. Oviduct pathology is a result of excessive PMN infiltration. Flow cytometric analyses demonstrate significantly reduced PMN infiltration to the genital tracts in IL-1 alpha and caspase-11 KO mice. However, T cell infiltration to the genital tracts is unchanged in both the groups, which reflected in normal infection clearance in IL-1 alpha and caspase-11 KO mice. These data suggest that activation of cell death pathways and local release of IL-1 alpha causes long-term damage to the oviducts during Chlamydia infection. [Supported by PHS funding NIAID AI067678 (UN)]