Innate immune recognition of flagellin limits systemic persistence of B rucella

Summary B rucella are facultative intracellular bacteria that cause chronic infections by limiting innate immune recognition. It is currently unknown whether B rucella   FliC flagellin, the monomeric subunit of flagellar filament, is sensed by the host during infection. Here, we used two mutants of B rucella 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 B rucella flagellin and the regulation of its synthesis and/or delivery into host cells are both part of the stealthy strategy of B rucella 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 B rucella and its host, which is characterized by a persistent infection with limited inflammatory pathology.