February 24, 2022
Keio University School of Medicine
An international collaborative research team—including Project Associate Professor Hideki Hara from the Department of Microbiology and Immunology, Keio University School of Medicine; Associate Professor Kosuke Tsuchiya from the Division of Immune and Inflammatory Regulation, Cancer Progression Control Institute, Kanazawa University; Professor Emeritus Masao Mitsuyama from Kyoto University; and Professor Gabriel Núñez from the Department of Pathology, University of Michigan School of Medicine, USA—has elucidated the relationship between the mechanism of immune responses that aggravate infectious diseases and toxin production. The results of this basic research are expected to lead to the development of new therapeutic methods that could replace existing treatments for infections, such as antimicrobial agents.
While immune responses are generally thought to work defensively against infections, recent studies have revealed the existence of inflammatory responses that worsen infections caused by pathogenic bacteria such as *Staphylococcus aureus* and intracellular parasitic bacteria, as well as by the novel coronavirus. Although this inflammatory response is strongly induced when pathogenic microorganisms cause an infection, its mechanism was not well understood.
In this study, the research team used *Listeria*, a typical intracellular parasitic bacterium, and found that its pathogenic toxin enhances an inflammatory response called the inflammasome by activating a kinase when it interacts with the cell membrane. Furthermore, they discovered that this pro-inflammatory activity is controlled by a single amino acid within this toxin, and that by simply mutating this amino acid, the bacterium can no longer activate the inflammasome, thereby losing its pathogenicity.
The results of this research were published in the online edition of the international scientific journal "Cell Reports" on February 22, 2022 (U.S. Eastern Standard Time).
Please see below for the full press release.