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.
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页码:2345 / 2352
页数:8
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