Interleukin-10 stimulates Coxiella burnetii replication in human monocytes through tumor necrosis factor down-modulation: role in microbicidal defect of Q fever.
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.
Unité des Rickettsies, CNRS UMR 6020, Université de la Méditerranée, Marseille, France.
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D015703:Antigens, CD / Q000378:metabolism; D001770:Blood Bactericidal Activity; D016997:Coxiella burnetii / Q000502:physiology*; D015536:Down-Regulation; D004697:Endocarditis, Bacterial / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D011778:Q Fever / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10