Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages

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-1 beta. 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-gamma is known to elicit M1 polarization, we assessed the effect of interferon-gamma on the fate of O. tsutsugamushi in macrophages. Exogenous interferon-gamma 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. (c) 2012 Elsevier Ltd. All rights reserved.