title: Autophagy adaptor protein p62/SQSTM1 and autophagy-related gene Atg5 mediate autophagosome formation in response to Mycobacterium tuberculosis infection in dendritic cells.
abstract: Mycobacterium tuberculosis is an intracellular pathogen that can survive within phagocytic cells by inhibiting phagolysosome biogenesis. However, host cells can control the intracellular M. tuberculosis burden by the induction of autophagy. The mechanism of autophagosome formation to M. tuberculosis has been well studied in macrophages, but remains unclear in dendritic cells. We therefore characterized autophagosome formation in response to M. tuberculosis infection in dendritic cells. Autophagy marker protein LC3, autophagy adaptor protein p62/SQSTM1 (p62) and ubiquitin co-localized to M. tuberculosis in dendritic cells. Mycobacterial autophagosomes fused with lysosomes during infection, and major histcompatibility complex class II molecules (MHC II) also localized to mycobacterial autophagosomes. The proteins p62 and Atg5 function in the initiation and progression of autophagosome formation to M. tuberculosis, respectively; p62 mediates ubiquitination of M. tuberculosis and Atg5 is involved in the trafficking of degradative vesicles and MHC II to mycobacterial autophagosomes. These results imply that the autophagosome formation to M. tuberculosis in dendritic cells promotes the antigen presentation of mycobacterial peptides to CD4(+) T lymphocytes via MHC II.
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Seto
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Tsujimura
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Horii
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Koide
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D001343:Autophagy / Q000276:immunology*; D000071187:Autophagy-Related Protein 5; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D015151:Immunoblotting; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism*; D009169:Mycobacterium tuberculosis; D010588:Phagosomes / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000071456:Sequestosome-1 Protein; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D006360:Heat-Shock Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse