Mycobacterium tuberculosis Lipoprotein MPT83 Induces Apoptosis of Infected Macrophages by Activating the TLR2/p38/COX-2 Signaling Pathway

摘要: Tuberculosis caused by Mycobacterium tuberculosis continues to pose a serious global health threat. The attenuated bovis bacillus Calmette-Guerin, as the only licensed vaccine, has limited protective efficacy against TB. development of more effective antituberculosis vaccines is urgent and demands for further identification understanding M. Ags. MPT83 (Rv2873), secreted mycobacterial lipoprotein, been applied into subunit vaccine shown effects infection in animals; however, underlying mechanism limited. In present study, we systematically studied effect on macrophage apoptosis constructing smegmatis strain overexpressing (MS_MPT83) purifying rMPT83 protein. We found that induced both human mouse macrophages. cyclooxygenase-2 (COX-2) expression at transcriptional protein levels macrophages, whereas silencing or inhibiting COX-2 blocked rMPT83-induced enhanced apoptotic response MS_MPT83 comparison with transfected pMV261 vector (MS_Vec), indicating required MPT83-induced apoptosis. Additionally, tlr2 deficiency led significant reduction expression, accompanied less macrophages stimulated infected MS_MPT83. Moreover, activation p38 accounted expression. Finally, lower bacteria burdens lungs spleens survival were observed mice i.v. compared MS_Vec. Taken together, our results established proapoptotic identified TLR2/p38/COX-2 axis