PMID- 22256790 OWN - NLM STAT- MEDLINE DCOM- 20120808 LR - 20120419 IS - 1462-5822 (Electronic) IS - 1462-5814 (Linking) VI - 14 IP - 5 DP - 2012 May TI - Coronin-1a inhibits autophagosome formation around Mycobacterium tuberculosis-containing phagosomes and assists mycobacterial survival in macrophages. PG - 710-27 LID - 10.1111/j.1462-5822.2012.01754.x [doi] AB - Mycobacterium tuberculosis is an intracellular bacterium that can survive within macrophages. Such survival is potentially associated with Coronin-1a (Coro1a). We investigated the mechanism by which Coro1a promotes the survival of M. tuberculosis in macrophages and found that autophagy was involved in the inhibition of mycobacterial survival in Coro1a knock-down (KD) macrophages. Fluorescence microscopy and immunoblot analyses revealed that LC3, a representative autophagic protein, was recruited to M. tuberculosis-containing phagosomes in Coro1a KD macrophages. Thin-section electron microscopy demonstrated that bacilli were surrounded by the multiple membrane structures in Coro1a KD macrophages. The proportion of LC3-positive mycobacterial phagosomes colocalized with p62/SQSTM1, ubiquitin or LAMP1 increased in Coro1a KD macrophages during infection. These results demonstrate the formation of autophagosomes around M. tuberculosis in Coro1a KD macrophages. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) was induced in response to M. tuberculosis infection in Coro1a KD macrophages, suggesting that Coro1a blocks the activation of the p38 MAPK pathway involved in autophagosome formation. LC3 recruitment to M. tuberculosis-containing phagosomes was also observed in Coro1a KD alveolar or bone marrow-derived macrophages. These results suggest that Coro1a inhibits autophagosome formation in alveolar macrophages, thereby facilitating M. tuberculosis survival within the lung. CI - (c) 2012 Blackwell Publishing Ltd. FAU - Seto, Shintaro AU - Seto S AD - Department of Infectious Diseases, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192, Japan. s-seto@hama-med.ac.jp FAU - Tsujimura, Kunio AU - Tsujimura K FAU - Koide, Yukio AU - Koide Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120214 PL - India TA - Cell Microbiol JT - Cellular microbiology JID - 100883691 RN - 0 (Microfilament Proteins) RN - 145420-64-0 (coronin proteins) SB - IM MH - Animals MH - Cell Line MH - Gene Knockdown Techniques MH - *Host-Pathogen Interactions MH - Immunoblotting MH - Macrophages/*microbiology/ultrastructure MH - Mice MH - Microbial Viability MH - Microfilament Proteins/genetics/*metabolism MH - Microscopy, Electron MH - Microscopy, Fluorescence MH - Mycobacterium tuberculosis/*pathogenicity/ultrastructure MH - Phagosomes/*microbiology/ultrastructure EDAT- 2012/01/20 06:00 MHDA- 2012/08/09 06:00 CRDT- 2012/01/20 06:00 PHST- 2012/01/20 06:00 [entrez] PHST- 2012/01/20 06:00 [pubmed] PHST- 2012/08/09 06:00 [medline] AID - 10.1111/j.1462-5822.2012.01754.x [doi] PST - ppublish SO - Cell Microbiol. 2012 May;14(5):710-27. doi: 10.1111/j.1462-5822.2012.01754.x. Epub 2012 Feb 14.