Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
Sci Rep. 2017 Oct 27;7(1):14224. doi: 10.1038/s41598-017-14640-1.
The pathogenesis of severe dengue remains unclear, particularly the mechanisms underlying the plasma leakage that results in hypovolaemic shock in a small proportion of individuals. Maximal leakage occurs several days after peak viraemia implicating immunological pathways. Skin is a highly vascular organ and also an important site of immune reactions with a high density of dendritic cells (DCs), macrophages and T cells. We obtained skin biopsies and contemporaneous blood samples from patients within 24 hours of onset of dengue shock syndrome (DSS), and from healthy controls. We analyzed cell subsets by flow cytometry, and soluble mediators and antibodies by ELISA; the percentage of migratory CD1a dermal DCs was significantly decreased in the DSS patients, and skin CD8 T cells were activated, but there was no accumulation of dengue-specific antibodies. Inflammatory monocytic cells were not observed infiltrating the skin of DSS cases on whole-mount histology, although CD14 cells disappeared from blood.
登革热重症的发病机制仍不清楚,尤其是少数患者发生低血容量性休克的血浆渗漏机制。最大渗漏发生在病毒血症峰值后数天,提示免疫途径参与其中。皮肤是一个高度血管化的器官,也是免疫反应的重要部位,有高密度的树突状细胞(DC)、巨噬细胞和 T 细胞。我们在登革热休克综合征(DSS)发病后 24 小时内从患者和健康对照者获得皮肤活检和同期血样。我们通过流式细胞术分析细胞亚群,通过 ELISA 分析可溶性介质和抗体;DSS 患者皮肤中迁移性 CD1a 真皮 DC 的比例显著下降,皮肤 CD8 T 细胞被激活,但没有积累登革热特异性抗体。全组织学观察并未发现炎症性单核细胞浸润 DSS 病例的皮肤,尽管血液中的 CD14 细胞消失。