Novel Receptor Protein for Short-Chain Fatty Acids Helps Elucidate Defense Mechanism Against Salmonella Infection
Nov. 2, 2020
Keio University School of Medicine Japan Agency for Medical Research and Development
A research team at Keio University has successfully identified apoptosis-associated speck-like protein (ASC), a novel receptor protein for short-chain fatty acids (SCFAs) that are produced by gastrointestinal bacteria, and discovered that ASC mediates enhancement of innate immunity to prevent Salmonella infection leading to food poisoning. The team was led by Assistant Professor Hitoshi Tsugawa, Associate Professor Yasuaki Kabe, and Professor Makoto Suematsu of the Department of Biochemistry, Keio University School of Medicine.
It is known that SCFAs are produced in large quantities through the breakdown of dietary fiber by gastrointestinal bacteria and are involved in the regulation of the immune system, but their molecular mechanism of action has remained unknown. In this study, the research team succeeded in identifying a human-derived receptor apoptosis-associated speck-like (ASC) protein that specifically binds to SCFAs using a proprietary drug receptor detection technology. ASC is also known to be a key adaptor protein in the activation of the inflammasome. The research team has clarified that SCFAs enhance the natural defenses of macrophages, a type of immunocompetent cells, by activating the inflammasome-forming ability of ASC. The team also found that this immunostimulatory effect contributes to protection against Salmonella bacteria, which causes food poisoning. The team observed that the survival of mouse models of Salmonella infection was significantly prolonged through the ingestion of water-soluble dietary fibers, which are broken down in the intestine to produce large amounts of SCFAs. These findings reveal a new regulatory mechanism by which SCFAs suppress Salmonella infection through inflammasome activation. They are expected to lead to the development of new treatments and prevention methods for defending against pathogen infection through the ingestion of food components such as the dietary fiber that produce SCFAs.
The results of this research were published on September 29, 2020 (PDT), in the online version of the scientific journal PLoS Biology.
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