Coxiella burnetii Induces Inflammatory Interferon-Like Signature in Plasmacytoid Dendritic Cells: A New Feature of Immune Response in Q Fever

伯氏考克斯体诱导浆细胞样树突状细胞产生炎症性干扰素样特征:Q热免疫反应的新特征

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作者:Mignane B Ka ,Soraya Mezouar ,Amira Ben Amara ,Didier Raoult ,Eric Ghigo ,Daniel Olive ,Jean-Louis Mege

Abstract

Plasmacytoid dendritic cells (pDCs) play a major role in antiviral immunity via the production of type I interferons (IFNs). There is some evidence that pDCs interact with bacteria but it is not yet clear whether they are protective or contribute to bacterial pathogenicity. We wished to investigate whether Coxiella burnetii, the agent of Q fever, interacts with pDCs. The stimulation of pDCs with C. burnetii increased the expression of activation and migratory markers (CD86 and CCR7) as determined by flow cytometry and modulated gene expression program as revealed by a microarray approach. Indeed, genes encoding for pro-inflammatory cytokines, chemokines, and type I INF were up-regulated. The up-regulation of type I IFN was correlated with an increase in IFN-α release by C. burnetii-stimulated pDCs. We also investigated pDCs in patients with Q fever endocarditis. Using flow cytometry and a specific gating strategy, we found that the number of circulating pDCs was significantly lower in patients with Q fever endocarditis as compared to healthy donors. In addition, the remaining circulating pDCs expressed activation and migratory markers. As a whole, our study identified non-previously reported activation of pDCs by C. burnetii and their modulation during Q fever. Keywords: Coxiella burnetii; Q fever; infection; interferon; plasmacytoid dendritic cells.

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