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=Volume 10 - 2019

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=Dengue virus (DENV) infection causes 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 reveal a distinct mechanism by which DENV induces tissue injury and vascular leakage through promoting interleukin-1β (IL-1β) activation. DENV facilitates IL-1β secretion in infected patients, mice, human peripheral blood mononuclear cells (PBMCs), mice bone marrow-derived macrophages (BMDMs), and monocyte-differentiated macrophages (THP-1) via activating the NLRP3 inflammasome. Moreover, IL-1β induces vascular leakage and tissue injury in interferon alpha/beta receptor 1 deficient C57BL/6 mice (IFNAR-/- C57BL/6), whereas interleukin-1 receptor antagonist (IL-1RA) inhibits IL-1β-induced vascular leakage and tissue injury in mice. Finally, recombinant IL-1β protein can induce directly vascular leakage and tissue injury in C57BL/6 mice. Therefore, this study demonstrates a major contribution of IL-1β to DENV-associated pathology, and suggests IL-1RA acting as a potential agent for the infectious diseases.