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

Masashi Kanayama, Makoto Inoue, Keiko Danzaki, Gianna Hammer, You-Wen He and Mari L. Shinohara ()
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Masashi Kanayama: Duke University Medical Center
Makoto Inoue: Duke University Medical Center
Keiko Danzaki: Duke University Medical Center
Gianna Hammer: Duke University Medical Center
You-Wen He: Duke University Medical Center
Mari L. Shinohara: Duke University Medical Center

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract 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 F4/80hi 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 F4/80hi macrophages, which express abundant A20 and contribute to the initiation of efficient innate immune responses.

Date: 2015
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DOI: 10.1038/ncomms6779

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