AUTHOR=Pan Pan , Zhang Qi , Liu Weiyong , Wang Wenbiao , Yu Zhenyang , Lao Zizhao , Zhang Wei , Shen Miaomiao , Wan Pin , Xiao Feng , Shereen Muhammad Adnan , Zhang Wen , Tan Qiuping , Liu Yuntao , Liu Xiaohong , Wu Kailang , Liu Yingle , Li Geng , Wu Jianguo 

TITLE=Dengue Virus Infection Activates Interleukin-1β to Induce Tissue Injury and Vascular Leakage

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02637

DOI=10.3389/fmicb.2019.02637

ISSN=1664-302X

ABSTRACT=<p>Dengue virus (DENV) infection causes several diseases ranging from dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome characterized by endothelial dysfunction, vascular leakage, and shock. Here, we identify a potential mechanism by which DENV induces tissue injury and vascular leakage by promoting the activation of interleukin (IL)-1β. DENV facilitates IL-1β secretion in infected patients, mice, human peripheral blood mononuclear cells (PBMCs), mouse bone marrow-derived macrophages (BMDMs), and monocyte-differentiated macrophages (THP-1) <italic>via</italic> activating the NLRP3 inflammasome. The accumulated data suggest that IL-1β probably induces vascular leakage and tissue injury in interferon-alpha/beta receptor 1 deficient C57BL/6 mice (<italic>IFNAR</italic><sup>–/–</sup> C57BL/6), whereas IL-1 receptor antagonist (IL-1RA) alleviates these effects of IL-1β. Finally, administration of recombinant IL-1β protein results in vascular leakage and tissue injury in C57BL/6 mice. Together, the accumulated results demonstrate that IL-1β contributes to DENV-associated pathology and suggest that IL-1RA acts as a potential agent for the treatment of DENV-associated diseases.</p>