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bioRxiv · 10.1101/2021.02.03.429556

Down Regulation Of IL-1β Secretion By TGF-β1 In Macrophages Infected With Dengue Virus

Ramirez-Aguero, B.·Serrato-Salas, J.·Montiel Hernandez, J. L.·Gonzalez-Christen, J.
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Abstract

Several pathogenic mechanisms have been linked to the severity of dengue virus infection, like viral cytotoxicity, underlying host genetics and comorbidities such as diabetes and dyslipidemia. It has been observed that patients with severe manifestations develop an uncontrolled immune response, with an increase in pro-inflammatory cytokines such as TNF, IL-1{beta}, IL-8, IL-6 and chemokines that damage the human microvascular endothelium, and also in anti-inflammatory cytokines IL-4, IL-10 and TGF-{beta}1. The role of TGF-{beta}1 on dengue is not clear; few studies have been published, and most of them from patient sera data, with both protective and pathological roles have described. The aim of this study was to evaluate the ability of TGF-{beta}1 to regulate the secretion of IL-1{beta} in macrophages infected by DENV using THP-1 cells treated with recombinant TGF-{beta}1 before or after DENV infection. By RT-PCR we did not observe a difference in IL-1{beta} expression between infected cells pretreated with TGF-{beta}1 and those that were not. However, secretion of IL-1{beta} was reduced only in cells stimulated with TGF-{beta}1 before infection, and not in those treated 2 hours post-infection. TGF-{beta}1 receptor blockage with SB505124 inhibitor, prior to the addition of TGF-{beta}1 and infection, abrogated the inhibitory effect of TGF-{beta}1. Our results suggest that DENV could regulate the function of TGF-{beta}1 on macrophages. This negative regulation of the TGF-{beta}1 pathway could be used by DENV to evade the immune response and could contribute to the immunopathology.

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Ramirez-Aguero, B., Serrato-Salas, J., Montiel Hernandez, J. L., Gonzalez-Christen, J.. 2021-02-03. Down Regulation Of IL-1β Secretion By TGF-β1 In Macrophages Infected With Dengue Virus. https://doi.org/10.1101/2021.02.03.429556

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