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

• DOI: 10.1371/journal.pbio.3000813
• Publication Date: 2020-09-29T17:24:12Z
• Authors: Hitoshi Tsugawa; Yasuaki Kabe; Ayaka Kanai; Yuki Sugiura; Shigeaki Hida; Shun’ichiro Tanig...; Toshio Takahashi; Hidenori Matsui; Zenta Yasukawa; Hiroyuki Itou; Keiyo Takubo; Hidekazu Suzuki; Kenya Honda; Hiroshi Handa; Makoto Suematsu
• Keywords: Salmonella enterica; Pyroptosis; NLRC4; Pyrin domain

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 of inflammasome complex, as a noncanonical SCFA receptor besides GPRs. SCFAs promoted activation in macrophages binding to its ASC PYRIN domain. Activated suppressed survival Salmonella enterica serovar Typhimurium (S. Typhimurium) pyroptosis and facilitated neutrophil recruitment promote bacterial elimination thus inhibit systemic dissemination the host. Administration or dietary fibers, which are fermented gut bacteria, significantly prolonged S. Typhimurium–infected mice through ASC-mediated activation. penetrated into inflammatory region infected mucosa protect against infection. This study provided evidence that suppress infection via activation, shedding new light on therapeutic activity fiber.