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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

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Author(s):
Case, Christopher L. [1] ; Kohler, Lara J. [1] ; Lima, Jonilson B. [2] ; Strowig, Till [3] ; de Zoete, Marcel R. [3] ; Flavell, Richard A. [3, 4] ; Zamboni, Dario S. [2] ; Roy, Craig R. [1]
Total Authors: 8
Affiliation:
[1] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT 06536 - USA
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP - Brazil
[3] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 - USA
[4] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 - USA
Total Affiliations: 4
Document type: Journal article
Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 110, n. 5, p. 1851-1856, JAN 29 2013.
Web of Science Citations: 139
Abstract

A flagellin-independent caspase-1 activation pathway that does not require NAIP5 or NRLC4 is induced by the intracellular pathogen Legionella pneumophila. Here we demonstrate that this pathway requires caspase-11. Treatment of macrophages with LPS up-regulated the host components required for this caspase-11 activation pathway. Activation by Legionella differed from caspase-11 activation using previously described agonists in that Legionella caspase-11 activation was rapid and required bacteria with a functional type IV secretion system called Dot/Icm. Legionella activation of caspase-11 induced pyroptosis by a mechanism independent of the NAIP/NLRC4 and caspase-1 axis. Legionella activation of caspase-11 stimulated activation of caspase-1 through NLRP3 and ASC. Induction of caspase-11 dependent responses occurred in macrophages deficient in the adapter proteins TRIF or MyD88 but not in macrophages deficient in both signaling factors. Although caspase-11 was produced in macrophages deficient in the type-I IFN receptor, there was a severe defect in caspase-11 dependent pyroptosis in these cells. These data indicate that macrophages respond to microbial signatures to produce proteins that mediate a capsase-11 response and that the caspase-11 system provides an alternative pathway for rapid detection of an intracellular pathogen capable of evading the canonical caspase-1 activation system that responds to bacterial flagellin. (AU)

FAPESP's process: 12/09363-6 - Molecular pathogenesis and subversion of host responses in infections with Legionella spp.
Grantee:Dario Simões Zamboni
Support Opportunities: Regular Research Grants