期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 50, 页码 13242-13247出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1710433114
关键词
inflammasome; NAIP; NLRC4; flagellin; type III secretion system
资金
- NIH National Cancer Institute [R01CA188034, P30-CA016520]
- NIH National Institute of General Medical Sciences [T32GM07229, R25GM071745]
- NIH National Institute of Allergy and Infectious Diseases [R01AI118861, R01AI123243]
- National Science Foundation [DGE-1321851]
- College Alumni Society Board of Managers and Presidents Undergraduate Research Grant
- College Alumni Society Pincus-Magaziner Family Undergraduate Research Grant
- Burroughs-Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases Award
Inflammasomes are cytosolic multiprotein complexes that initiate host defense against bacterial pathogens by activating caspase-1-dependent cytokine secretion and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) activate the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4) inflammasome upon sensing components of the type III secretion system (T3SS) and flagellar apparatus. NAIP1 recognizes the T3SS needle protein, NAIP2 recognizes the T3SS inner rod protein, and NAIP5 and NAIP6 recognize flagellin. In contrast, humans encode a single functional NAIP, raising the question of whether human NAIP senses one or multiple bacterial ligands. Previous studies found that human NAIP detects both flagellin and the T3SS needle protein and suggested that the ability to detect both ligands was achieved by multiple isoforms encoded by the single human NAIP gene. Here, we show that human NAIP also senses the Salmonella Typhimurium T3SS inner rod protein PrgJ and that T3SS inner rod proteins from multiple bacterial species are also detected. Furthermore, we show that a single human NAIP isoform is capable of sensing the T3SS inner rod, needle, and flagellin. Our findings indicate that, in contrast to murine NAIPs, promiscuous recognition of multiple bacterial ligands is conferred by a single human NAIP.
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