Innate immune recognition of flagellin limits systemic persistence of Brucella

Matthieu 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

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Summary: Brucella are facultative intracellular bacteria that cause chronic infections by limiting innate immune recognition. It is currently unknown whether BrucellaFliC 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 NLRC4in 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. © 2012 John Wiley & Sons Ltd.

Original languageEnglish
Pages (from-to)942-960
Number of pages19
JournalCellular microbiology
Issue number6
Publication statusPublished - 1 Jun 2013


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