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Innate immune recognition of flagellin limits systemic persistence of Brucella.

Abstract
Brucella are facultative intracellular bacteria that cause chronic infections by limiting innate immune recognition. It is currently unknown whether Brucella FliC flagellin, the monomeric subunit of flagellar filament, is sensed by the host during infection. Here, we used two mutants of Brucella melitensis, either lacking or overexpressing flagellin, to show that FliC hinders bacterial replication in vivo. The use of cells and mice genetically deficient for different components of inflammasomes suggested that FliC was a target of the cytosolic innate immune receptor NLRC4 in vivo but not in macrophages in vitro where the response to FliC was nevertheless dependent on the cytosolic adaptor ASC, therefore suggesting a new pathway of cytosolic flagellin sensing. However, our work also suggested that the lack of TLR5 activity of Brucella flagellin and the regulation of its synthesis and/or delivery into host cells are both part of the stealthy strategy of Brucella towards the innate immune system. Nevertheless, as a flagellin-deficient mutant of B. melitensis wasfound to cause histologically demonstrable injuries in the spleen of infected mice, we suggested that recognition of FliC plays a role in the immunological stand-off between Brucella and its host, which is characterized by a persistent infection with limited inflammatory pathology.
AuthorsMatthieu Terwagne, Jonathan Ferooz, Hortensia G Rolán, Yao-Hui Sun, Vidya Atluri, Mariana N Xavier, Luigi Franchi, Gabriel Núñez, Thomas Legrand, Richard A Flavell, Xavier De Bolle, Jean-Jacques Letesson, Renée M Tsolis
JournalCellular microbiology (Cell Microbiol) Vol. 15 Issue 6 Pg. 942-960 (Jun 2013) ISSN: 1462-5822 [Electronic] India
PMID23227931 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2012 John Wiley & Sons Ltd.
Chemical References
  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Ipaf protein, mouse
  • Toll-Like Receptor 5
  • Flagellin
Topics
  • Animals
  • Apoptosis Regulatory Proteins (metabolism)
  • Brucella melitensis (immunology, metabolism, pathogenicity)
  • Brucellosis (metabolism, pathology, physiopathology)
  • Calcium-Binding Proteins (metabolism)
  • Cell Line
  • Colon (microbiology, pathology)
  • Disease Models, Animal
  • Female
  • Flagellin (genetics, immunology, metabolism)
  • Humans
  • Immunity, Innate (physiology)
  • In Vitro Techniques
  • Macrophages (microbiology, pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mutation (genetics)
  • Spleen (microbiology, pathology)
  • Toll-Like Receptor 5 (metabolism)

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