AUTHOR=Conti Filippo , Boucherit Nicolas , Baldassarre Veronica , Trouplin Virginie , Toman Rudolf , Mottola Giovanna , Mege Jean-Louis , Ghigo Eric 

TITLE=Coxiella burnetii lipopolysaccharide blocks p38α-MAPK activation through the disruption of TLR-2 and TLR-4 association

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=4

YEAR=2015

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2014.00182

DOI=10.3389/fcimb.2014.00182

ISSN=2235-2988

ABSTRACT=<p>To survive in macrophages, <italic>Coxiella burnetii</italic> hijacks the activation pathway of macrophages. Recently, we have demonstrated that <italic>C. burnetii</italic>, via its lipopolysaccharide (LPS), avoids the activation of p38α-MAPK through an antagonistic engagement of Toll-like receptor (TLR)-4. We investigated the fine-tuned mechanism leading to the absence of activation of the p38α-MAPK despite TLR-4 engagement. In macrophages challenged with LPS from the avirulent variants of <italic>C. burnetii</italic>, TLR-4 and TLR-2 co-immunoprecipitated. This association was absent in cells challenged by the LPS of pathogenic <italic>C. burnetii</italic>. The disruption makes TLRs unable to signal during the recognition of the LPS of pathogenic <italic>C. burnetii</italic>. The disruption of TLR-2 and TLR-4 was induced by the re-organization of the macrophage cytoskeleton by <italic>C. burnetii</italic> LPS. Interestingly, blocking the actin cytoskeleton re-organization relieved the disruption of the association TLR-2/TLR-4 by pathogenic <italic>C. burnetii</italic> and rescued the p38α-MAPK activation by <italic>C. burnetii</italic>. We elucidated an unexpected mechanism allowing pathogenic <italic>C. burnetii</italic> to avoid macrophage activation by the disruption of the TLR-2 and TLR-4 association.</p>