Mast Cell-Derived Proteases Induce Endothelial Permeability and Vascular Damage in Severe Fever with Thrombocytopenia Syndrome

• DOI: 10.1128/spectrum.01294-22
• Publication Date: 2022-05-25T13:00:43Z
• Authors: Yu-Na Wang; Yun-Fa Zhang; Xue-Fang Peng; Hong-Han Ge; Gang Wang; Heng Ding; Yue Li; Shuang Li; Ling-Yu Zhang; Jing-Tao Zhang; Hao Li; Xiao-Ai Zhang; Wei Liu
• Keywords: Vascular permeability

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic acquired by tick bites. Whether mast cells (MCs), the body's first line of defense against pathogens, might influence immunity or pathogenesis during SFTS virus (SFTSV) infection remained unknown. Here, we found that SFTSV can cause MC and degranulation, resulting in release vasoactive mediators, chymase, tryptase, which directly act on endothelial cells, break tight junctions threaten integrity microvascular barrier, leading to hyperpermeability human cells. Local activation MCs (degranulation) MC-specific proteases-facilitated damage were observed mouse models. When proteases injected subcutaneously into back skin mice, signs capillary leakage a dose-dependent manner. proteases, tryptase tested serum collected at acute phase patients, higher level significantly correlated fatal outcomes. By performing receiver operator characteristic curve (ROC) analysis, chymase was determined as biomarker area under value 0.830 (95% CI = 0.745 0.915) for predicting outcomes SFTS. Our findings highlight importance SFTSV-induced disease progression outcome. An role clinical prognosis blocking potential drug target proposed. IMPORTANCE We revealed pathogenic response infection. The study also identifies biomarkers could differentiate patients risk outcome SFTS, well novel therapeutic targets management These shed light other viral diseases similar host pathology