HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages
Macrophages are derived from monocytes in the bone marrow and play an important role in anti-viral innate immune responses. Macrophages produce cytokines such as interferons and IL-10 upon viral infection to modulate anti-viral immune responses. Type I interferons (IFNs) promote anti-viral defense....
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2020-08-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01776/full |
id |
doaj-a2d966f5a3094128977938bf5b58d628 |
---|---|
record_format |
Article |
spelling |
doaj-a2d966f5a3094128977938bf5b58d6282020-11-25T03:40:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01776565300HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in MacrophagesYan Wang0Yan Wang1Ke Wang2Jian Fu3Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, United StatesDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, United StatesMacrophages are derived from monocytes in the bone marrow and play an important role in anti-viral innate immune responses. Macrophages produce cytokines such as interferons and IL-10 upon viral infection to modulate anti-viral immune responses. Type I interferons (IFNs) promote anti-viral defense. IL-10 is a suppressor cytokine that down-regulates anti-viral immune responses. HDAC6 is a tubulin deacetylase that can modulate microtubule dynamics and microtubule-mediated cell signaling pathways. In the present study, we investigated the potential role of HDAC6 in macrophage anti-viral responses by examining poly (I:C)-induced IFN-β and IL-10 production in mouse bone marrow-derived macrophages (BMDMs). We also investigated the role of HDAC6 in poly (I:C)-induced anti-viral signaling such as TBK1, GSK-3β, and Akt activation in mouse BMDMs. Our data showed that HDAC6 deletion enhanced poly (I:C)-induced INF-β expression in macrophages by up-regulating TBK1 activity and eliminating the inhibitory regulation of GSK-3β. Furthermore, HDAC6 deletion inhibited poly (I:C)-induced suppressor cytokine IL-10 production in the BMDMs, which was associated with the inhibition of Akt activation. Our results suggest that HDAC6 modulates IFN-β and IL-10 production in macrophages through its regulation of TBK1, GSK-3β, and Akt signaling. HDAC6 could act as a suppressor of anti-viral innate immune responses in macrophages.https://www.frontiersin.org/article/10.3389/fimmu.2020.01776/fullinnate immunityinfectioncytokineacetylationmicrotubule |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yan Wang Yan Wang Ke Wang Jian Fu |
spellingShingle |
Yan Wang Yan Wang Ke Wang Jian Fu HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages Frontiers in Immunology innate immunity infection cytokine acetylation microtubule |
author_facet |
Yan Wang Yan Wang Ke Wang Jian Fu |
author_sort |
Yan Wang |
title |
HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages |
title_short |
HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages |
title_full |
HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages |
title_fullStr |
HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages |
title_full_unstemmed |
HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages |
title_sort |
hdac6 mediates poly (i:c)-induced tbk1 and akt phosphorylation in macrophages |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-08-01 |
description |
Macrophages are derived from monocytes in the bone marrow and play an important role in anti-viral innate immune responses. Macrophages produce cytokines such as interferons and IL-10 upon viral infection to modulate anti-viral immune responses. Type I interferons (IFNs) promote anti-viral defense. IL-10 is a suppressor cytokine that down-regulates anti-viral immune responses. HDAC6 is a tubulin deacetylase that can modulate microtubule dynamics and microtubule-mediated cell signaling pathways. In the present study, we investigated the potential role of HDAC6 in macrophage anti-viral responses by examining poly (I:C)-induced IFN-β and IL-10 production in mouse bone marrow-derived macrophages (BMDMs). We also investigated the role of HDAC6 in poly (I:C)-induced anti-viral signaling such as TBK1, GSK-3β, and Akt activation in mouse BMDMs. Our data showed that HDAC6 deletion enhanced poly (I:C)-induced INF-β expression in macrophages by up-regulating TBK1 activity and eliminating the inhibitory regulation of GSK-3β. Furthermore, HDAC6 deletion inhibited poly (I:C)-induced suppressor cytokine IL-10 production in the BMDMs, which was associated with the inhibition of Akt activation. Our results suggest that HDAC6 modulates IFN-β and IL-10 production in macrophages through its regulation of TBK1, GSK-3β, and Akt signaling. HDAC6 could act as a suppressor of anti-viral innate immune responses in macrophages. |
topic |
innate immunity infection cytokine acetylation microtubule |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.01776/full |
work_keys_str_mv |
AT yanwang hdac6mediatespolyicinducedtbk1andaktphosphorylationinmacrophages AT yanwang hdac6mediatespolyicinducedtbk1andaktphosphorylationinmacrophages AT kewang hdac6mediatespolyicinducedtbk1andaktphosphorylationinmacrophages AT jianfu hdac6mediatespolyicinducedtbk1andaktphosphorylationinmacrophages |
_version_ |
1724532887677566976 |