Institute of Development, Aging and Cancer, Tohoku University

Research

Seminars and Symposia

IDAC Seminar, 8 July 2015

Secretariat, Alumni Association, IDAC
Date Wednesday,8 July 2015, 17:00〜
Room Seminar-shitsu 1, IDAC Research building 7F
Title Inflammasomes coordinate pyroptosis and NK cytotoxicity to prevent the Purple Death
Speaker Edward A. Miao
Affiliation The University of North Carolina at Chapel Hill
Person-in-charge Wataru Shoji, ext. 92-4734
Masafumi Nakayama,  022-795-5259
Abstract 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)