Mycobacterium tuberculosisis protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA

• DOI: 10.1073/pnas.1707792114
• Publication Date: 2017-10-03T00:40:29Z
• Authors: Stefan Köster; Sandeep Upadhyay; Pallavi Chandra; Kadamba Papavinas...; Guozhe Yang; Amir Hassan; Steven J. Grigsby; Ekansh Mittal; Heidi S. Park; Victoria Jones; Fong-Fu Hsu; Mary Jackson; Christopher M. Sa...; Jennifer A. Philips
• Keywords: Male; autophagy; 570; 610; Nitric Oxide Synthase Type II; Mice, SCID; Microbiology; Mice; Bacterial Proteins; Phagocytosis; Phagosomes; M. tuberculosis; Autophagy; Animals; Tuberculosis; Immunology and Infectious Disease; Mice, Knockout; NADPH oxidase; Macrophages; Mycobacterium tuberculosis; LC3-associated phagocytosis; LytR-CpsA-Psr; 3. Good health; Cellular and Molecular Physiology; Mice, Inbred C57BL; Host-Pathogen Interactions; NADPH Oxidase 2; Female; Reactive Oxygen Species; Microtubule-Associated Proteins

SignificanceMycobacterium tuberculosis(Mtb), the causative agent of the disease tuberculosis, grows in macrophages, cells that normally kill bacteria. Recent work has defined a macrophage pathway called “LC3-associated phagocytosis” (LAP) that can eliminate other microbes. LAP is characterized by the recruitment of NADPH oxidase to phagosomes, followed by phagosomal association with LC3 and delivery of the bacteria to a degradative lysosome. Here, we show that LAP does not effectively clear Mtb. The ability of Mtb to inhibit LAP and therefore cause disease depends upon CpsA, a member of the LytR-CpsA-Psr (LCP) protein family, which has previously been implicated in cell-wall metabolism. We demonstrate that Mtb CpsA plays an unexpected role in antagonizing host innate immunity by inhibiting NADPH oxidase and LAP.