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Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.

Publication ,  Journal Article
Kanayama, M; Inoue, M; Danzaki, K; Hammer, G; He, Y-W; Shinohara, ML
Published in: Nat Commun
January 22, 2015

Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert antimicrobial responses. Here we report a role of autophagy in an early host antifungal response by enhancing NFκB activity through A20 sequestration. Enhancement of NFκB activation is achieved by autophagic depletion of A20, an NFκB inhibitor, in F4/80(hi) macrophages in the spleen, peritoneum and kidney. We show that p62, an autophagic adaptor protein, captures A20 to sequester it in the autophagosome. This allows the macrophages to release chemokines to recruit neutrophils. Indeed, mice lacking autophagy in myeloid cells show higher susceptibility to Candida albicans infection due to impairment in neutrophil recruitment. Thus, at least in the specific aforementioned tissues, autophagy appears to break A20-dependent suppression in F4/80(hi) macrophages, which express abundant A20 and contribute to the initiation of efficient innate immune responses.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 22, 2015

Volume

6

Start / End Page

5779

Location

England

Related Subject Headings

  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Spleen
  • Signal Transduction
  • Peritoneum
  • Neutrophils
  • NF-kappa B p50 Subunit
  • Myeloid Cells
  • Microtubule-Associated Proteins
  • Microscopy, Confocal
  • Mice, Knockout
 

Citation

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Kanayama, M., Inoue, M., Danzaki, K., Hammer, G., He, Y.-W., & Shinohara, M. L. (2015). Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity. Nat Commun, 6, 5779. https://doi.org/10.1038/ncomms6779
Kanayama, Masashi, Makoto Inoue, Keiko Danzaki, Gianna Hammer, You-Wen He, and Mari L. Shinohara. “Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.Nat Commun 6 (January 22, 2015): 5779. https://doi.org/10.1038/ncomms6779.
Kanayama M, Inoue M, Danzaki K, Hammer G, He Y-W, Shinohara ML. Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity. Nat Commun. 2015 Jan 22;6:5779.
Kanayama, Masashi, et al. “Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.Nat Commun, vol. 6, Jan. 2015, p. 5779. Pubmed, doi:10.1038/ncomms6779.
Kanayama M, Inoue M, Danzaki K, Hammer G, He Y-W, Shinohara ML. Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity. Nat Commun. 2015 Jan 22;6:5779.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 22, 2015

Volume

6

Start / End Page

5779

Location

England

Related Subject Headings

  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Spleen
  • Signal Transduction
  • Peritoneum
  • Neutrophils
  • NF-kappa B p50 Subunit
  • Myeloid Cells
  • Microtubule-Associated Proteins
  • Microscopy, Confocal
  • Mice, Knockout