BioProject

Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, a bacterium that mainly infects endothelial cells in vitro and in vivo. More...

Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, a bacterium that mainly infects endothelial cells 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 showed here that O. tsutsugamushi intensively replicated within human monocyte-derived macrophages. Bacterial organisms stimulated the expression of a large panel of genes including type I interferon, interferon-stimulated, inflammatory, apoptosis-related genes and induced an M1-type gene response in macrophages. This transcriptional signature was accompanied by functional consequences such as the release of inflammatory cytokines such as Tumor Necrosis Factor and interleukin-gamma. Live O. tsutsugamushi organisms were necessary for type I interferon response and, to a lesser degree, to inflammatory response. As interferon-gamma is known to elicit M1 polarization, we assessed the effect of interferon-gamma on O. tsutsugamushi fate in macrophages. Exogenous interferon-gamma partly 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 and that interferon-gamma may be useful as an adjuvant treatment of patients with scrub typhus. Overall design: Macrophages (4 × 10.5 cells per assay) were incubated with O. tsutsugamushi at a bacterium-to-cell ratio of 20:1 for 8 hours. RNA samples (four samples per experimental condition) were processed for microarray analysis. Less...