Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes.
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...
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ftdoajarticles:oai:doaj.org/article:731cc867bdd44cb9ac864bdaad4e0ddf 2023-05-15T15:12:17+02:00 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 2014-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003320 https://doaj.org/article/731cc867bdd44cb9ac864bdaad4e0ddf EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4239119?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003320 https://doaj.org/article/731cc867bdd44cb9ac864bdaad4e0ddf PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e3320 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003320 2022-12-31T08:44:01Z 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.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.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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 11 e3320 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Tsung-Ting Tsai Yi-Jui Chuang Yee-Shin Lin Chih-Peng Chang Shu-Wen Wan Sheng-Hsiang Lin Chia-Ling Chen Chiou-Feng Lin Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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.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.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. |
format |
Article in Journal/Newspaper |
author |
Tsung-Ting Tsai Yi-Jui Chuang Yee-Shin Lin Chih-Peng Chang Shu-Wen Wan Sheng-Hsiang Lin Chia-Ling Chen Chiou-Feng Lin |
author_facet |
Tsung-Ting Tsai Yi-Jui Chuang Yee-Shin Lin Chih-Peng Chang Shu-Wen Wan Sheng-Hsiang Lin Chia-Ling Chen Chiou-Feng Lin |
author_sort |
Tsung-Ting Tsai |
title |
Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes. |
title_short |
Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes. |
title_full |
Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes. |
title_fullStr |
Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes. |
title_full_unstemmed |
Antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of IL-10 production in monocytes. |
title_sort |
antibody-dependent enhancement infection facilitates dengue virus-regulated signaling of il-10 production in monocytes. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003320 https://doaj.org/article/731cc867bdd44cb9ac864bdaad4e0ddf |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e3320 (2014) |
op_relation |
http://europepmc.org/articles/PMC4239119?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003320 https://doaj.org/article/731cc867bdd44cb9ac864bdaad4e0ddf |
op_doi |
https://doi.org/10.1371/journal.pntd.0003320 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
11 |
container_start_page |
e3320 |
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1766342995937853440 |