Coxiella burnetii Blocks Intracellular Interleukin-17 Signaling in Macrophages

Tatiana M Clemente, Minal Mulye, Anna V Justis, Srinivas Nallandhighal, Tuan M Tran, Stacey D Gilk

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Coxiella burnetii  is an obligate intracellular bacterium and the etiological agent of Q fever. Successful host cell infection requires the  Coxiella  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  Coxiella  T4BSS effector proteins, we determined the transcriptome of murine alveolar macrophages infected with a  Coxiella  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  Coxiella  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  Coxiella  infection is unknown. We found that IL-17 kills intracellular  Coxiella  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  Il1a Il1b , and  Tnfa , the chemokine genes  Cxcl2  and  Ccl5 , and the antimicrobial protein gene  Lcn2  We further confirmed that the  Coxiella  T4BSS downregulates macrophage CXCL2/macrophage inflammatory protein 2 and CCL5/RANTES protein levels following IL-17 stimulation. Together, these data suggest that  Coxiella  downregulates IL-17 signaling in a T4BSS-dependent manner in order to escape the macrophage immune response.
Original languageAmerican English
JournalInfection and Immunity
StatePublished - 2018


  • Coxiella burnetii
  • IL-17
  • innate immunity
  • macrophage
  • type 4 secretion


  • Medicine and Health Sciences

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