Coxiella burnetii lipopolysaccharide blocks p38α-MAPK activation through the disruption of TLR-2 and TLR-4 association
Coxiella burnetii lipopolysaccharide blocks p38α-MAPK activation through the disruption of TLR-2 and TLR-4 association
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DOI：
10.3389/fcimb.2014.00182
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发表时间：
2015-01-06
影响因子：
5.7
通讯作者：
Ghigo, Eric
中科院分区：
文献类型：
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作者：
Conti, Filippo;Boucherit, Nicolas;Ghigo, Eric
为了在巨噬细胞中存活，贝氏柯克斯体劫持了巨噬细胞的活化途径。最近，我们证明了C。贝氏菌通过其脂多糖（LPS），通过Toll样受体（TLR）-4的拮抗作用避免p38 α-MAPK的活化。我们研究了导致尽管TLR-4参与但p38 α-MAPK不激活的微调机制。在巨噬细胞中，用C.贝氏体、TLR-4和TLR-2共免疫沉淀。这种关联在被致病性C的LPS攻击的细胞中不存在。伯内特氏菌这种破坏使得TLR在识别致病性C.伯内特氏菌TLR-2和TLR-4的破坏是由C.贝氏菌有趣的是，阻断肌动蛋白细胞骨架重组减轻了致病性C.贝氏梭菌对p38 α-MAPK的激活有明显的抑制作用。伯内特氏菌我们阐明了一个意想不到的机制，使致病性C。Burnetii以避免通过破坏TLR-2和TLR-4结合而激活巨噬细胞。
To survive in macrophages, Coxiella burnetii hijacks the activation pathway of macrophages. Recently, we have demonstrated that C. burnetii, via its lipopolysaccharide (LPS), avoids the activation of p38 alpha-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 p38 alpha-MAPK despite TLR-4 engagement. In macrophages challenged with LPS from the avirulent variants of C. burnetii, TLR-4 and TLR-2 co-immunoprecipitated. This association was absent in cells challenged by the LPS of pathogenic C. burnetii. The disruption makes TLRs unable to signal during the recognition of the LPS of pathogenic C. burnetii. The disruption of TLR-2 and TLR-4 was induced by the re-organization of the macrophage cytoskeleton by C. burnetii LPS. Interestingly, blocking the actin cytoskeleton re-organization relieved the disruption of the association TLR-2/TLR-4 by pathogenic C. burnetii and rescued the p38 alpha-MAPK activation by C. burnetii. We elucidated an unexpected mechanism allowing pathogenic C. burnetii to avoid macrophage activation by the disruption of the TLR-2 and TLR-4 association.