Pseudomonas Aeruginosa Activates Caspase 1 Through Ipaf

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Feb 8

PMID 18256184

Citations 169

Authors

Edward A Miao

Robert K Ernst

Monica Dors

Dat P Mao

Alan Aderem

Affiliations

Soon will be listed here.

Abstract

The innate immune system encodes cytosolic Nod-like receptors (NLRs), several of which activate caspase 1 processing and IL-1beta and IL-18 secretion. Macrophages respond to Salmonella typhimurium infection by activating caspase 1 through the NLR Ipaf. This activation is mediated by cytosolic flagellin through the activity of the virulence-associated type III secretion system (T3SS). We demonstrate here that Pseudomonas aeruginosa activates caspase 1 and induces IL-1beta secretion in infected macrophages. While live, virulent P. aeruginosa activate IL-1beta secretion through caspase 1 and Ipaf, strains that have mutations in the T3SS or in flagellin did not. Ipaf-dependent caspase 1 activation could be recapitulated by delivering P. aeruginosa flagellin to the macrophage cytosol. We examined the role of Naip5 in P. aeruginosa-induced caspase 1 activation by using A/J (Naip5-deficient) compared with C57BL/6 and BALB/c (Naip5-sufficient) macrophages and observed that A/J macrophages secrete IL-1beta in response to P. aeruginosa, S. typhimurium, and Listeria monocytogenes infection, as well as in response to cytosolic flagellin, but at slightly reduced levels. Thus, Ipaf-dependent detection of cytosolic flagellin is a conserved mechanism by which macrophages detect the presence of pathogens that use T3SS.

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