Role of IL-33 in chronic pulmonary mycobacterial infection (MPF7P.705)

Abstract

IL-33 is a recently identified IL-1 family cytokine that promotes type 2 immune responses by signaling through the receptor complex consisted of ST2 and IL-1RAcP. Recent study using ST2 KO mice showed that IL-33 mediated signaling is required for the development of innate and adaptive immune responses against pulmonary Cryptococcus neoformans infection, suggesting involvement of IL-33/IL33R system in pulmonary cell-mediated immunity. In contrast, the ST2 KO mice showed normal protective immunity against pulmonary Mycobacterium tuberculosis (Mtb) infection. In this study, we analyzed role of IL-33 in host defense against chronically infected Mtb using IL-33 KO mice. The survival rate of the IL-33 KO mice was similar to that of the wild-type (WT) mice during 1 year observation period. Bacterial burdens of various organs of the IL-33 KO mice on the day 120 were nearly the same as that of the WT mice. In the infected lungs, inflammatory cytokine such as IFN-γ, TNF-α and IL-6, production of the IL-33 KO mice were similar to that of the WT mice. This result indicated that the generation of Th1 cells was not affected in the IL-33 KO mice infected with Mtb. Furthermore, the size of granulomatous lesionss in the lungs of the IL-33 KO mice were similar in comparison to the granulomas that of the WT mice on day 250 of infection. These data strongly support the notion that the lack of IL-33 neither suppress nor enhances protective immunity in the lung after mycobacterial infection.