Coxiella burnetii is an obligate intracellular bacterium, responsible for Q fever, which survives in macrophages by interfering with their microbicidal competence. As functional polarization of macrophages is critical for their microbicidal activity, we studied the activation program of monocyte‐derived macrophages (MDM) stimulated with C. burnetii. This program was markedly distinct from that induced by lipopolysaccharides (LPS), a canonical inducer of M1 polarization. Indeed, C. burnetii up‐regulated the expression of genes associated with M2 polarization, including TGF‐β1, IL‐1 receptor antagonist (IL‐1ra), CCL18, the mannose receptor and arginase‐1, and only up‐regulated the expression of two genes associated with M1 polarization, namely IL‐6 and CXCL8. In contrast, C. burnetii down‐regulated the expression of genes associated with M1 polarization such as TNF, CD80, CCR7 and TLR‐2. Functional analyses showed that C. burnetii‐stimulated MDM produced high levels of TGF‐β1 and CCL18, and expressed the mannose receptor and arginase‐1, the latter being associated with the prevention of nitric oxide production by MDM. Finally, C. burnetii induced the release of IL‐6 and CXCL8 at a lower level than LPS‐stimulated MDM. Our results suggest that C. burnetii stimulated an atypical M2 activation program that may account for the persistence of C. burnetii in macrophages.

Supporting Information for this article is available at http://www.wiley‐vch.de/contents/jc_2040/2008/37917_s.pdf