Critical role of Annexin A1 in protection against pulmonary Mycobacterium tuberculosis infection. (P3320)

Abstract

Abstract Annexin1 is a 37kDa protein with wide spectrum of biological activity. Although there are data emphasizing on anti-inflammatory role of Annexin1 in inflammatory diseases, little is known about its role in pathogenesis of tuberculosis. Recently, it has been described the involvement of Annexin1 in the formation of apoptotic envelope, generation of “eat me” signal and activation of Tcells. As phagocytosis of apoptotic vesicles from Mycobacterium tuberculosis (Mtb) infected macrophages is one of the main sources of antigens for CD8T cells via cross-presentation, we hypothesized that impaired capacity of Annexin1-/-DC in cross-presentation increases host susceptibility to Mtb infection. We found that Annexin1-/-mice were severely susceptible to Mtb infection. High levels of pulmonary bacterial burden and mortality in Annexin1-/-mice were associated with reduced antigen-specific CD8T cell response in the lungs. This reduced response was not due to an intrinsic role of Annexin1 in macrophage apoptosis or T cell activation as generation of chimeric mice in which only T cells were deficient in Annexin1 did not show impairment in Tcell mediated immunity or protection against Mtb infection. Interestingly, both in vitro and in vivo, Annexin1-/-DC demonstrated a significantly reduced capacity to cross-present antigens to CD8Tcells. Together, these data identify Annexin1 as a central player in protective immunity against Mtb infection, by regulating the power of DC in cross-presentation.