Coxiella burnetii, the agent of Q fever, stimulates an atypical M2 activation program in human macrophages.
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-beta1, 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-beta1 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.
Benoit
Marie
M
Unité des Rickettsies, CNRS UMR 6020, IFR 48, Université de la Méditerranée, Faculté de Médecine, Marseille, France.
Barbarat
Bernadette
B
Bernard
Alain
A
Olive
Daniel
D
Mege
Jean-Louis
JL
D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016997:Coxiella burnetii / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D011778:Q Fever / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics
D008070:Lipopolysaccharides