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Pseudomonas aeruginosa activates caspase 1 through Ipaf

Open access
Miao, Edward A., Ernst, Robert K., Dors, Monica, Mao, Dat P., Aderem, Alan·2008·Proceedings of the National Academy of Sciences

Abstract

The innate immune system encodes cytosolic Nod-like receptors (NLRs), several of which activate caspase 1 processing and IL-1β 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-1β secretion in infected macrophages. While live, virulent P. aeruginosa activate IL-1β 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-1β 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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Metadata

Authors
Miao, E. A., Ernst, R. K., Dors, M., Mao, D. P., & Aderem, A.
Venue
Proceedings of the National Academy of Sciences
Published
2008-02-19
Volume
105
Issue
7
Pages
2562-2567
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2020683003
Cited by
297
References
7
FWCI
11.54
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Pseudomonas aeruginosa activates caspase 1 through Ipaf. https://app.cochat.ai/papers/10.1073/pnas.0712183105
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Miao, E. A., Ernst, R. K., Dors, M., Mao, D. P., & Aderem, A. (2008). Pseudomonas aeruginosa activates caspase 1 through Ipaf. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0712183105

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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