CD157 Confers Host Resistance to Mycobacterium tuberculosis via TLR2-CD157-PKCzeta-Induced Reactive Oxygen Species Production

Abstract

Tuberculosis, a chronic bacterial disease caused by Mycobacterium tuberculosis , remains a major global health problem. CD157, a dual-function receptor and β-NAD + -metabolizing ectoenzyme, promotes cell polarization, regulates chemotaxis induced through the high-affinity fMLP receptor, and controls transendothelial migration. The role of CD157 in TB pathogenesis remains unknown. In this study, we find that both mRNA and protein levels of CD157 are significantly increased in TB. Deficiency of CD157 impaired host defense against M. tuberculosis infection both in vivo and in vitro , which is mediated by an interaction among CD157, TLR2, and PKCzeta. This interaction facilitates M. tuberculosis -induced macrophagic ROS production, which enhances macrophage bactericidal activity. Interestingly, the sCD157 level in plasma is reversibly associated with MDM M. tuberculosis killing activity. By uncovering the role of CD157 in pathogenesis of TB for the first time, our work demonstrated that application of soluble CD157 might be an effective strategy for host-directed therapy against TB.