Wiwit TantibhedhyangkulAmira Ben AmaraJulien TextorisLaurent GorvelEric GhigoChristian CapoJean Louis MegeUnite de Recherche sur les Maladies Infectieuses et Tropicales emergentesMahidol University2018-10-192018-10-192013-02-01Microbial Pathogenesis. Vol.55, No.1 (2013), 55-6310961208088240102-s2.0-84876126444https://repository.li.mahidol.ac.th/handle/20.500.14594/31971Scrub 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. © 2012 Elsevier Ltd.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1016/j.micpath.2012.10.001