Coxiella burnetii Blocks Intracellular Interleukin-17 Signaling in Macrophages.

is an obligate intracellular bacterium and the etiological agent of Q fever. Successful host cell infection requires the type IVB secretion system (T4BSS), which translocates bacterial effector proteins across the vacuole membrane into the host cytoplasm, where they manipulate a variety of cell processes. To identify host cell targets of T4BSS effector proteins, we determined the transcriptome of murine alveolar macrophages infected with a T4BSS effector mutant. We identified a set of inflammatory genes that are significantly upregulated in T4BSS mutant-infected cells compared to mock-infected cells or cells infected with wild-type (WT) bacteria, suggesting that T4BSS effector proteins downregulate the expression of these genes. In addition, the interleukin-17 (IL-17) signaling pathway was identified as one of the top pathways affected by the bacteria. While previous studies demonstrated that IL-17 plays a protective role against several pathogens, the role of IL-17 during infection is unknown. We found that IL-17 kills intracellular in a dose-dependent manner, with the T4BSS mutant exhibiting significantly more sensitivity to IL-17 than WT bacteria. In addition, quantitative PCR confirmed the increased expression of IL-17 downstream signaling genes in T4BSS mutant-infected cells compared to WT- or mock-infected cells, including the proinflammatory cytokine genes , , and , the chemokine genes and , and the antimicrobial protein gene We further confirmed that the T4BSS downregulates macrophage CXCL2/macrophage inflammatory protein 2 and CCL5/RANTES protein levels following IL-17 stimulation. Together, these data suggest that downregulates IL-17 signaling in a T4BSS-dependent manner in order to escape the macrophage immune response.