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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere3000813
JournalPLoS biology
Volume18
Issue number9
DOIs
Publication statusPublished - 2020 Sep

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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