Autophagy adaptor protein p62/SQSTM1 and autophagy-related gene Atg5 mediate autophagosome formation in response to Mycobacterium tuberculosis infection in dendritic cells

PLoS One. 2013 Dec 23;8(12):e86017. doi: 10.1371/journal.pone.0086017. eCollection 2013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Antibodies, Monoclonal
  • Autophagy / immunology*
  • Autophagy-Related Protein 5
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Heat-Shock Proteins / immunology
  • Heat-Shock Proteins / metabolism*
  • Immunoblotting
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / immunology
  • Microtubule-Associated Proteins / metabolism*
  • Mycobacterium tuberculosis*
  • Phagosomes / immunology*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Sequestosome-1 Protein
  • Tuberculosis / immunology*


  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Heat-Shock Proteins
  • MAP1LC3 protein, mouse
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse

Grant support

This work was supported in part by Grants-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science; the Health and Labour Science Research Grants for Research into Emerging and Reemerging Infectious Diseases from the Ministry of Health, Labour and Welfare of Japan; and the United States-Japan Cooperative Medical Science Committee. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.