Pseudomonas aeruginosa activates caspase 1 through Ipaf

TitlePseudomonas aeruginosa activates caspase 1 through Ipaf
Publication TypeJournal Article
Year of Publication2008
AuthorsMiao EA, Ernst RK, Dors M, Mao DP, Aderem A
JournalProc Natl Acad Sci U S A
Date PublishedFeb 19
PubMed Central ID2268176
KeywordsApoptosis Regulatory Proteins/*metabolism, Calcium-Binding Proteins/*metabolism, Caspase 1/*metabolism, Cells, Cultured, Cytosol/metabolism, Enzyme Activation, Flagellin/pharmacology, Interleukin-1beta/secretion, Macrophages/drug effects/metabolism/secretion, Neuronal Apoptosis-Inhibitory Protein/metabolism, Protein Transport, Pseudomonas aeruginosa/*metabolism
AbstractThe 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.