東北大学加齢医学研究所 加齢医学研究拠点 | Institute of Development, Aging and Cancer, Tohoku University

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◇平成27年7月8日(水)加齢研研究員会セミナ-のご案内
日時: 平成27年7月8日(水)午後5時〜
場所: 加齢研実験研究棟7階 セミナー室1
演題: インフラマソームは炎症性細胞死(パイロトーシス)とNK活性を協調させて重篤な細菌感染症を防御する
講師: エドワード ミアオ
所属: ノースカロライナ大学
担当: 東海林亙(プロジェクト研究推進研究分野・内線92-4734)
連絡先:中山勝文  022-795-5259
要旨: Defective neutrophils in chronic granulomatous disease (CGD) cause susceptibility not only to extracellular, but also to intracellular infections. However, microbes must first be ejected from intracellular niches to expose them to neutrophil attack. This can be accomplished by pyroptosis. We therefore hypothesized that inflammasomes detect certain CGD pathogens upstream of the neutrophil killing step. Here, we discover one such ubiquitous environmental bacterium, Chromobacterium violaceum, whose extreme virulence is fully counteracted by the NLRC4 inflammasome. Caspase-1 protects via two parallel pathways that eliminate intracellular replication niches: pyroptosis, and IL-18 driven NK cell cytotoxicity. These insights suggested a therapeutic approach; administration of exogenous IL-18 restored perforin-dependent cytotoxicity during infection by the inflammasome evasive bacterium Listeria monocytogenes. (Ref: Hagar JA et al. Science, 2013; Aachoui Y et al, Science, 2013; Maltez VI and Miao EA, Trends Immunol, 2014)

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