Autophagy enhances NF kappa B activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity

作者：Kanayama Masashi; Inoue Makoto; Danzaki Keiko; Hammer Gianna; He You Wen; Shinohara Mari L^*

来源：Nature Communications, 2015, 6(1): 5779.

DOI：10.1038/ncomms6779

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 NF kappa B activity through A20 sequestration. Enhancement of NF kappa B activation is achieved by autophagic depletion of A20, an NF kappa B 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.

• 出版日期2015-1