title: Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages.
abstract: Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, a bacterium that primarily infects endothelial cells both in vitro and in vivo. Evidence suggests that the interaction of O. tsutsugamushi with myeloid cells may play a pivotal role in O. tsutsugamushi infection. We demonstrated that O. tsutsugamushi replicated within human monocyte-derived macrophages. Bacteria stimulated the expression of a large number of genes, including type I interferon genes, interferon-stimulated genes, inflammation-associated genes and apoptosis-related genes, and the release of inflammatory cytokines such as Tumor Necrosis Factor and interleukin-1β. In addition, O. tsutsugamushi induced an M1-type genetic program in macrophages. O. tsutsugamushi viability was required for the type I interferon response and, to a lesser degree, for the inflammatory response. As interferon-γ is known to elicit M1 polarization, we assessed the effect of interferon-γ on the fate of O. tsutsugamushi in macrophages. Exogenous interferon-γ partially inhibited O. tsutsugamushi replication within macrophages. Our results suggest that the inflammatory response induced by O. tsutsugamushi may account for the local and systemic inflammation observed in scrub typhus.
authors.affiliation: Aix-Marseille Université, URMITE, UMR CNRS, IRD, Inserm, France. wiwit167@yahoo.co.th
authors.forename: Wiwit
authors.initials: W
authors.lastname: Tantibhedhyangkul
authors.forename: Amira
authors.initials: A
authors.lastname: Ben Amara
authors.forename: Julien
authors.initials: J
authors.lastname: Textoris
authors.forename: Laurent
authors.initials: L
authors.lastname: Gorvel
authors.forename: Eric
authors.initials: E
authors.lastname: Ghigo
authors.forename: Christian
authors.initials: C
authors.lastname: Capo
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D012285:Orientia tsutsugamushi / Q000276:immunology* / Q000502:physiology; D012612:Scrub Typhus / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D007370:Interferon Type I; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma