Interleukin-10 stimulates Coxiella burnetii replication in human monocytes through tumor necrosis factor down-modulation:: Role in microbicidal defect of Q fever

被引:74
作者
Ghigo, E [1 ]
Capo, C [1 ]
Raoult, D [1 ]
Mege, JL [1 ]
机构
[1] Univ Mediterranee, Fac Med Marseille, Unite Rickettsies, CNRS,UMR 6020, F-13385 Marseille 05, France
关键词
D O I
10.1128/IAI.69.4.2345-2352.2001
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, an obligate intracellular bacterium, is the agent of Q fever, The chronic form of the disease is associated with the overproduction of interleukin-10 and deficient C. burnetii killing by monocytes. We hypothesized that the replication of C. burnetii inside-monocytes requires a macrophage-deactivating cytokine such as interleukin-10, In the absence of interleukin-10, C. burnetii survived but did not replicate in monocytes, C. burnetii replication (measured 15 days) was induced in interleukin-10-treated monocytes, This effect of interleukin-10 is specific since transforming growth factor beta1 had no effect on bacterial replication. C. burnetii replication involves the down-modulation of tumor necrosis factor (TNF) release. First, interleukin-10 suppressed C. burnetii-stimulated production of TNF, Second, the addition of recombinant TNF to interleukin-10-treated monocytes inhibited bacterial replication. Third, the incubation of infected monocytes with neutralizing anti-TNF antibodies favored C. burnetii replication. On the other hand, deficient C. burnetii killing by monocytes from patients with chronic Q fever involves interleukin-10. Indeed, C. burnetii replication was observed in monocytes from patients with Q fever endocarditis, but not in those from patients with acute Q fever. Bacterial replication was inhibited by neutralizing anti-interleukin-10 antibodies. As monocytes from patients with endocarditis overproduced interleukin-10, the defective bacterial killing is likely related to endogenous interleukin-10. These results suggest that interleukin-10 enables monocytes to support C. burnetii replication and to favor the development of chronic Q fever.
引用
收藏
页码:2345 / 2352
页数:8
相关论文
共 39 条
[21]  
Irikura VM, 1999, INFECT IMMUN, V67, P1901
[22]  
IZZO AA, 1993, CLIN EXP IMMUNOL, V94, P507, DOI 10.1111/j.1365-2249.1993.tb08226.x
[23]   IL-4, IL-10 and IFN-gamma have distinct, but interacting, effects on differentiation-induced changes in TNF-alpha and TNF receptor release by cultured human monocytes [J].
Joyce, DA ;
Steer, JH .
CYTOKINE, 1996, 8 (01) :49-57
[24]  
Kaufman SHE., 1999, FUNDAMENTAL IMMUNOLO, P1335
[25]  
KOSTER FT, 1985, J IMMUNOL, V135, P1067
[26]   Regulation of immune responses by TGF-β [J].
Letterio, JJ ;
Roberts, AB .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :137-161
[27]  
MALEFYT RD, 1991, J EXP MED, V174, P1209
[28]   Q fever [J].
Maurin, M ;
Raoult, D .
CLINICAL MICROBIOLOGY REVIEWS, 1999, 12 (04) :518-+
[29]  
NAKAGAWARA A, 1983, J IMMUNOL METHODS, V56, P261
[30]  
OSWALD IP, 1992, J IMMUNOL, V148, P3578