[WS2] 腸内微生物叢の今

[WS2-5] グラム陽性菌によるNLRP6インフラマソーム活性化機序の解析

○原 英樹¹，Gabriel Nunez²，吉村 昭彦¹ (¹慶應義塾大学医学部微生物学免疫学，²ミシガン大学医学部病理学)

Immune cells, such as macrophages, neutrophils, and dendritic cells, express various receptors including Toll-like receptors and Nod-like receptors. These receptors sense extracellular and intracellular ligands, respectively, to induce inflammatory responses. Some intracellular receptors recruit adaptor ASC (apoptosis-associated speck-like protein containing caspase recruitment domain) and protease pro-caspase-1 to form inflammasome complex and activate caspase-1. Among them, NLRP6 (Nod-like receptor family pyrin domain containing 6) highly expresses in the intestine, however, regulatory mechanisms and functions of NLRP6 were not elucidated well. In this study, we found that Listeria monocytogenes, a Gram-positive pathogen capable of causing food poisoning, activate inflammasome responses through NLRP6. Interestingly, NLRP6 deficient mice harbored less bacterial loads compared with wild-type mice after orally infection with the bacterium. To identify a bacterial ligand for NLRP6, we stimulated macrophages with bacterial extracts and found that lipoteichoic acid, a molecule produced by Gram-positive bacteria, binds and activates NLRP6 inflammasome. These results reveal a previously unrecognized innate immunity pathway triggered by cytosolic lipoteichoic acid that is sensed by NLRP6 and exacerbates Gram-positive pathogen infection.