Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Graduate Program in Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Front Cell Infect Microbiol. 2021 Jul 22;11:683017. doi: 10.3389/fcimb.2021.683017. eCollection 2021.
Scrub typhus, caused by , is a common systemic infection in Asia. Delay in diagnosis and treatment can lead to vasculitis in the visceral organs and other complications. The mechanisms that drive endothelial activation and the inflammatory response in infection remain unknown. In addition, the interaction between monocytes and endothelial cells is still unclear. Here we demonstrate that -infected human dermal microvascular endothelial cells produced moderate levels of chemokines and low levels of IL-6 and IFN-β, but not TNF or IL-1β. Recombinant TNF and cytokine-rich supernatants from infected monocytes markedly enhanced chemokine production in infected endothelial cells. We also show that TNF and monocyte supernatants, but not infection of endothelial cells , upregulated the endothelial cell surface expression of ICAM-1, E-selectin, and tissue factor. This finding was consistent with the inability of to induce cytokine secretion from endothelial cells. The upregulation of surface molecules after stimulation with monocyte supernatants was significantly reduced by neutralizing anti-TNF antibodies. These results suggest that endothelial cell activation and response are mainly mediated by inflammatory cytokines secreted from monocytes.
恙虫病是由恙虫病东方体引起的一种常见的全身性感染。诊断和治疗的延误可能导致内脏器官的血管炎和其他并发症。导致恙虫病东方体感染中内皮细胞激活和炎症反应的机制尚不清楚。此外，单核细胞与内皮细胞之间的相互作用仍不清楚。在这里，我们证明感染人类皮肤微血管内皮细胞产生中等水平的趋化因子和低水平的 IL-6 和 IFN-β，但不产生 TNF 或 IL-1β。重组 TNF 和来自感染单核细胞的细胞因子丰富的上清液显著增强了感染内皮细胞中趋化因子的产生。我们还表明，TNF 和单核细胞上清液，但不是内皮细胞感染，上调了内皮细胞表面 ICAM-1、E-选择素和组织因子的表达。这一发现与恙虫病东方体不能诱导内皮细胞分泌细胞因子一致。用抗 TNF 抗体中和后，单核细胞上清液刺激后表面分子的上调显著减少。这些结果表明，内皮细胞的激活和反应主要是由单核细胞分泌的炎症细胞因子介导的。
