Short-chain fatty acids bind to apoptosisassociated speck-like protein to activate inflammasome complex to prevent Salmonella infection

Hitoshi Tsugawa, Yasuaki Kabe, Ayaka Kanai, Yuki Sugiura, Shigeaki Hida, Taniguchi Shun'ichiro Taniguchi, Toshio Takahashi, Hidenori Matsui, Zenta Yasukawa, Hiroyuki Itou, Keiyo Takubo, Hidekazu Suzuki, Kenya Honda, Hiroshi Handa, Makoto Suematsu

研究成果: Article査読

抄録

Short-chain fatty acids (SCFAs) produced by gastrointestinal microbiota regulate immune responses, but host molecular mechanisms remain unknown. Unbiased screening using SCFA-conjugated affinity nanobeads identified apoptosis-associated speck-like protein (ASC), an adaptor protein of inflammasome complex, as a noncanonical SCFA receptor besides GPRs. SCFAs promoted inflammasome activation in macrophages by binding to its ASC PYRIN domain. Activated inflammasome suppressed survival of Salmonella enterica serovar Typhimurium (S. Typhimurium) in macrophages by pyroptosis and facilitated neutrophil recruitment to promote bacterial elimination and thus inhibit systemic dissemination in the host. Administration of SCFAs or dietary fibers, which are fermented to SCFAs by gut bacteria, significantly prolonged the survival of S. Typhimurium-infected mice through ASCmediated inflammasome activation. SCFAs penetrated into the inflammatory region of the infected gut mucosa to protect against infection. This study provided evidence that SCFAs suppress Salmonella infection via inflammasome activation, shedding new light on the therapeutic activity of dietary fiber.

本文言語English
論文番号e3000813
ジャーナルPLoS biology
18
9
DOI
出版ステータスPublished - 2020 9

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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