title: IFN-gamma-mediated control of Coxiella burnetii survival in monocytes: the role of cell apoptosis and TNF.
abstract: The treatment of infectious diseases caused by intracellular bacteria, such as Q fever, may benefit from cytokines acting on macrophages. Monocytic THP-1 cells were infected with Coxiella burnetii, the etiological agent of Q fever, and then treated with IFN-gamma. While C. burnetii multiplied in untreated monocytes, IFN-gamma reduced bacterial viability after 24 h of treatment and reached maximum inhibition after 96 h. IFN-gamma also affected the viability of infected cells. Cell death resulted from apoptosis; occurring 24 h after the addition of IFN-gamma, it reached a maximum after 48 h and was followed by necrosis. Reactive oxygen intermediates were not required for C. burnetii killing, since monocytes from patients with chronic granulomatous disease were microbicidal in response to IFN-gamma. The role of cytokines was also investigated. IFN-gamma elicited a moderate release of IL-1beta in infected monocytes. Moreover, the IL-1 receptor antagonist did not affect C. burnetii survival, suggesting that IL-1beta was not involved in the bacterial killing induced by IFN-gamma. TNF was involved in IFN-gamma-induced killing of C. burnetii and cell death. IFN-gamma induced mRNA expression and sustained secretion of TNF. Neutralizing Abs to TNF as well as Abs directed against TNF receptors I and II, significantly prevented IFN-gamma-dependent killing of C. burnetii and cell death. These results suggest that IFN-gamma promotes the killing of C. burnetii in monocytes through an apoptotic mechanism mediated in part by TNF.
authors.affiliation: Unité des Rickettsies, Université de la Méditerranée, Centre National de la Recherche Scientifique, Faculté de Médecine, Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Dellacasagrande
authors.forename: C
authors.initials: C
authors.lastname: Capo
authors.forename: D
authors.initials: D
authors.lastname: Raoult
authors.forename: J L
authors.initials: JL
authors.lastname: Mege
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D003381:Coxiella / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D007739:L Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000382:microbiology* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*