Coxiella burnetti, the agent of Q fever, stimulates an atypical M2 activation program in human macrophages

被引:87
作者
Benoit, Marie [1 ]
Barbarat, Bernadette [2 ]
Bernard, Alain [3 ]
Olive, Daniel [2 ]
Mege, Jean-Louis [1 ]
机构
[1] Univ Aix Marseille 2, CNRS, UMR 6020, IFR 48,Unite Rickettsies,Fac Med, F-13385 Marseille 5, France
[2] Inst J Paoli I Calmettes, INSERM, UMR 599, Inst Cancerol Marseille, F-13009 Marseille, France
[3] Hop Archet, INSERM, U576, Nice, France
关键词
bacterial infections; chemokines; cytokines; innate immunity; macrophages;
D O I
10.1002/eji.200738067
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-beta 1, 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-beta 1 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.
引用
收藏
页码:1065 / 1070
页数:6
相关论文
共 30 条
[1]   Regulation of immune responses by L- arginine metabolism [J].
Bronte, V ;
Zanovello, P .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (08) :641-654
[2]  
Capo C, 1999, J IMMUNOL, V163, P6078
[3]   Protection of insulin secreting cells from nitric oxide induced cellular damage by crosslinked hemoglobin [J].
Chae, SY ;
Lee, M ;
Kim, SW ;
Bae, YH .
BIOMATERIALS, 2004, 25 (05) :843-850
[4]   αvβ3 integrin and bacterial lipopolysaccharide are involved in Coxiella burnetii-stimulated production of tumor necrosis factor by human monocytes [J].
Dellacasagrande, J ;
Ghigo, E ;
Hammami, SME ;
Toman, R ;
Raoult, D ;
Capo, C ;
Mege, JL .
INFECTION AND IMMUNITY, 2000, 68 (10) :5673-5678
[5]   IFN-γ-induced apoptosis and microbicidal activity in monocytes harboring the intracellular bacterium Coxiella burnetii require membrane TNF and homotypic cell adherence [J].
Dellacasagrande, J ;
Ghigo, E ;
Raoult, D ;
Capo, C ;
Mege, JL .
JOURNAL OF IMMUNOLOGY, 2002, 169 (11) :6309-6315
[6]   IL-16 is critical for Tropheryma whipplei replication in Whipple's disease [J].
Desnues, B ;
Raoult, D ;
Mege, JL .
JOURNAL OF IMMUNOLOGY, 2005, 175 (07) :4575-4582
[7]   Protective role of interleukin-6 during Yersinia enterocolitica infection is mediated through the modulation of inflammatory cyokines [J].
Dube, PH ;
Handley, SA ;
Lewis, J ;
Miller, VL .
INFECTION AND IMMUNITY, 2004, 72 (06) :3561-3570
[8]   Biochemical and functional characterization of three activated macrophage populations [J].
Edwards, Justin P. ;
Zhang, Xia ;
Frauwirth, Kenneth A. ;
Mosser, David M. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 80 (06) :1298-1307
[9]   Interleukin-4 induces Coxiella burnetii replication in human monocytes but not in macrophages [J].
Ghigo, E ;
Imbert, G ;
Capo, C ;
Raoult, D ;
Mege, JL .
RICKETTSIOLOGY: PRESENT AND FUTURE DIRECTIONS, 2003, 990 :450-459
[10]   Coxiella burnettii survival in THP-1 monocytes involves the impairment of phagosome maturation:: IFN-γ mediates its restoration and bacterial killing [J].
Ghigo, E ;
Capo, C ;
Tung, CH ;
Raoult, D ;
Gorvel, JP ;
Mege, JL .
JOURNAL OF IMMUNOLOGY, 2002, 169 (08) :4488-4495