Abstract
Apoptosis can potently defend against intracellular pathogens by directly killing microbes and eliminating their replicative niche. However, the reported ability of Mycobacterium tuberculosis to restrict apoptotic pathways in macrophages invitro has led to apoptosis being dismissed as a host-protective process in tuberculosis despite a lack of invivo evidence. Here we define crucial invivo functions of the death receptor-mediated and BCL-2-regulated apoptosis pathways in mediating protection against tuberculosis by eliminating distinct populations of infected macrophages and neutrophils and priming Tcell responses. We further show that apoptotic pathways can be targeted therapeutically with clinical-stage compounds thatantagonize inhibitor of apoptosis (IAP) proteins to promote clearance of M.tuberculosis in mice. These findings reveal that any inhibition of apoptosis by M.tuberculosis is incomplete invivo, advancing our understanding of host-protective responses to tuberculosis (TB) and revealing host pathways that may be targetable for treatment of disease.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
