Abstract
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 language | English |
|---|---|
| Pages (from-to) | 942-960 |
| Number of pages | 19 |
| Journal | Cellular microbiology |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1 Jun 2013 |
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Innate immune recognition of flagellin limits systemic persistence of Brucella. / Terwagne, Matthieu; Ferooz, Jonathan; Rolán, Hortensia G.; Sun, Yao Hui; Atluri, Vidya; Xavier, Mariana N.; Franchi, Luigi; Núñez, Gabriel; Legrand, Thomas; Flavell, Richard A.; De Bolle, Xavier; Letesson, Jean-Jacques; Tsolis, Renée M.
In: Cellular microbiology, Vol. 15, No. 6, 01.06.2013, p. 942-960.Research output: Contribution to journal › Article
TY - JOUR
T1 - Innate immune recognition of flagellin limits systemic persistence of Brucella
AU - Terwagne, Matthieu
AU - Ferooz, Jonathan
AU - Rolán, Hortensia G.
AU - Sun, Yao Hui
AU - Atluri, Vidya
AU - Xavier, Mariana N.
AU - Franchi, Luigi
AU - Núñez, Gabriel
AU - Legrand, Thomas
AU - Flavell, Richard A.
AU - De Bolle, Xavier
AU - Letesson, Jean-Jacques
AU - Tsolis, Renée M.
N1 - © 2012 Blackwell Publishing Ltd.
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84877833564&partnerID=8YFLogxK
U2 - 10.1111/cmi.12088
DO - 10.1111/cmi.12088
M3 - Article
C2 - 23227931
VL - 15
SP - 942
EP - 960
JO - Cellular microbiology
JF - Cellular microbiology
SN - 1462-5814
IS - 6
ER -