Antibody-Dependent Enhancement Infection Facilitates Dengue Virus-Regulated Signaling of IL-10 Production in Monocytes

Tsung Ting Tsai, Yi Jui Chuang, Yee Shin Lin, Chih Peng Chang, Shu Wen Wan, Sheng Hsiang Lin, Chia Ling Chen, Chiou Feng Lin

研究成果: Article同行評審

33 引文 斯高帕斯(Scopus)

摘要

Interleukin (IL)-10 levels are increased in dengue virus (DENV)-infected patients with severe disorders. A hypothetical intrinsic pathway has been proposed for the IL-10 response during antibody-dependent enhancement (ADE) of DENV infection; however, the mechanisms of IL-10 regulation remain unclear.

These results demonstrate that, in monocytes, IL-10 production is regulated by ADE through both an extrinsic and an intrinsic pathway, all involving a Syk-regulated PI3K/PKB/GSK-3β/CREB pathway, and both of which impact viral replication.

We found that DENV infection and/or attachment was sufficient to induce increased expression of IL-10 and its downstream regulator suppressor of cytokine signaling 3 in human monocytic THP-1 cells and human peripheral blood monocytes. IL-10 production was controlled by activation of cyclic adenosine monophosphate response element-binding (CREB), primarily through protein kinase A (PKA)- and phosphoinositide 3-kinase (PI3K)/PKB-regulated pathways, with PKA activation acting upstream of PI3K/PKB. DENV infection also caused glycogen synthase kinase (GSK)-3β inactivation in a PKA/PI3K/PKB-regulated manner, and inhibition of GSK-3β significantly increased DENV-induced IL-10 production following CREB activation. Pharmacological inhibition of spleen tyrosine kinase (Syk) activity significantly decreased DENV-induced IL-10 production, whereas silencing Syk-associated C-type lectin domain family 5 member A caused a partial inhibition. ADE of DENV infection greatly increased IL-10 expression by enhancing Syk-regulated PI3K/PKB/GSK-3β/CREB signaling. We also found that viral load, but not serotype, affected the IL-10 response. Finally, modulation of IL-10 expression could affect DENV replication.

原文English
期刊PLoS neglected tropical diseases
8
發行號11
DOIs
出版狀態Published - 2014

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

指紋 深入研究「Antibody-Dependent Enhancement Infection Facilitates Dengue Virus-Regulated Signaling of IL-10 Production in Monocytes」主題。共同形成了獨特的指紋。

引用此