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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02637

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

 Pan Pan1, Qi Zhang1, Weiyong Liu1,  Wenbiao Wang2, Zizhao Lao3, Wei Zhang3, Miaomiao Shen1, Pin Wan1, Feng Xiao1, Muhammad A. Shereen1, Wen Zhang4, Quiping Tan4, Yuntao Liu5, Xiaohong Liu3, Kailang Wu1, Yingle Liu1,  Geng Li3 and  Jianguo Wu1*
  • 1Wuhan University, China
  • 2Jinan University, China
  • 3Guangzhou University of Chinese Medicine, China
  • 4Other, China
  • 5Guangdong Provincial Hospital of Chinese Medicine, China

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.

Keywords: Dengue virus, DENV, Inflammatory Response, Interleukin-1 receptor antagonist, interleukine-1beta, NLRP3 inflammasome, Vascular Leakage

Received: 27 Jun 2019; Accepted: 30 Oct 2019.

Copyright: © 2019 Pan, Zhang, Liu, Wang, Lao, Zhang, Shen, Wan, Xiao, Shereen, Zhang, Tan, Liu, Liu, Wu, Liu, Li and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jianguo Wu, Wuhan University, Wuhan, 430072, Hubei Province, China, jwu@whu.edu.cn