Aix-Marseille Université, URMITE, UMR CNRS, IRD, Inserm, France.
Microb Pathog. 2013 Feb;55:55-63. doi: 10.1016/j.micpath.2012.10.001. Epub 2012 Oct 23.
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.
恙虫病是一种由恙虫东方体引起的危及生命的疾病，该细菌在体外和体内主要感染内皮细胞。有证据表明，恙虫东方体与髓样细胞的相互作用可能在恙虫东方体感染中起关键作用。我们证明恙虫东方体在人单核细胞衍生的巨噬细胞内复制。细菌刺激了大量基因的表达，包括 I 型干扰素基因、干扰素刺激基因、炎症相关基因和凋亡相关基因，以及炎症细胞因子如肿瘤坏死因子和白细胞介素-1β的释放。此外，恙虫东方体诱导巨噬细胞中 M1 型遗传程序。I 型干扰素反应和炎症反应在一定程度上需要恙虫东方体的存活。由于干扰素-γ已知能引发 M1 极化，我们评估了干扰素-γ对巨噬细胞中恙虫东方体命运的影响。外源性干扰素-γ部分抑制了巨噬细胞内恙虫东方体的复制。我们的结果表明，恙虫东方体诱导的炎症反应可能解释了恙虫病中观察到的局部和全身炎症。
