Earlier protective response and milder clinical course of Mycobacterium bovis BCG infection in mice lacking an adapter molecule CARD9 (55.6)

Abstract

Abstract CARD9 plays a crucial role as an adaptor molecule in signal transduction triggered through C-type lectin receptors that are known to recognize polysaccharides from various fungal microorganisms. In this study, we examined the role of CARD9 in the host defense to Mycobacterium bovis BCG that has polysaccharide cell-wall components such as lipoarabinomannan. C57BL/6 (WT) and CARD9 knockout (KO) mice were infected intratracheally with M. bovis BCG (Tokyo strain) per mouse. The number of viable bacterium, cytokine synthesis and histopathological findings in lungs were evaluated. CARD9KO mice cleared more bacteria in lungs than WT mice on day 28 after infection. In a histopathological analysis, the lung tissues from CARD9KO mice showed poorer granuloma formation and fewer bacilli in lungs than WT mice on days 14 and 28 after infection. The levels of IFN-γ, a key cytokine for the host defense to this infection, in the bronchoalveolar lavage fluids and its expression in T, NK and γδ T cells on day 7 were increased in CARD9KO mice compared to those in WT mice, although the production of this cytokine was significantly reduced in Card9KO mice on day 28. By contrast, the expression of IL-17A in lungs was not much different between WT and CARD9KO mice. These results indicate that CARD9 is dispensable for elimination of M. bovis BCG and granulomatous response, which suggests a complicated mechanism involved in the role of this molecule in the earlier host response to M. bovis BCG.