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Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection

BACKGROUND: Infection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated. Cytokines, which broadly also include chemokines and growth factors, have been shown to play a role in protective immunity as well as DENV and CHIK...

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Autores principales: Dhenni, Rama, Yohan, Benediktus, Alisjahbana, Bachti, Lucanus, Anton, Riswari, Silvita Fitri, Megawati, Dewi, Haryanto, Sotianingsih, Gampamole, Dekrit, Hayati, Rahma F., Sari, Kartika, Witari, Ni Putu Diah, Myint, Khin Saw Aye, Sasmono, R. Tedjo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254284/
https://www.ncbi.nlm.nih.gov/pubmed/34215212
http://dx.doi.org/10.1186/s12879-021-06339-6
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author Dhenni, Rama
Yohan, Benediktus
Alisjahbana, Bachti
Lucanus, Anton
Riswari, Silvita Fitri
Megawati, Dewi
Haryanto, Sotianingsih
Gampamole, Dekrit
Hayati, Rahma F.
Sari, Kartika
Witari, Ni Putu Diah
Myint, Khin Saw Aye
Sasmono, R. Tedjo
author_facet Dhenni, Rama
Yohan, Benediktus
Alisjahbana, Bachti
Lucanus, Anton
Riswari, Silvita Fitri
Megawati, Dewi
Haryanto, Sotianingsih
Gampamole, Dekrit
Hayati, Rahma F.
Sari, Kartika
Witari, Ni Putu Diah
Myint, Khin Saw Aye
Sasmono, R. Tedjo
author_sort Dhenni, Rama
collection PubMed
description BACKGROUND: Infection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated. Cytokines, which broadly also include chemokines and growth factors, have been shown to play a role in protective immunity as well as DENV and CHIKV pathogenesis. However, differences in cytokine response to both viruses remain poorly understood, especially in patients from countries where both viruses are endemic. Our study is therefore aimed to provide a comparative profiling of cytokine response induced by acute DENV and CHIKV infections in patients with similar disease stages and in experimental in vitro infections. METHODS: By using multiplex immunoassay, we compared host cytokine profiles between acute CHIKV and DENV infections by analysing serum cytokine levels of IL-1α, IL-4, IL-5, IL-8, IL-13, RANTES, MCP-3, eotaxin, PDGF-AB/BB, and FGF-2 from the sera of acute chikungunya and dengue fever patients. We further investigated the cytokine profile responses using experimental in vitro CHIKV and DENV infections of peripheral blood mononuclear cells (PBMCs). RESULTS: We found that both CHIKV and DENV-infected patients had an upregulated level of IL-8 and IL-4, with the highest IL-4 level observed in DENV-2 infected patients. Higher IL-8 level was also correlated with lower platelet count in dengue patients. IL-13 and MCP-3 downregulation was observed only in chikungunya patients, while conversely PDGF-AB/BB and FGF-2 downregulation was unique in dengue patients. Age-associated differential expression of IL-13, MCP-3, and IL-5 was also observed, while distinct kinetics of IL-4, IL-8, and FGF-2 expression between CHIKV and DENV-infected patients were identified. Furthermore, the unique pattern of IL-8, IL-13 and MCP-3, but not IL-4 expression was also recapitulated using experimental in vitro infection in PBMCs. CONCLUSIONS: Taken together, our study identified common cytokine response profile characterized by upregulation of IL-8 and IL-4 between CHIKV and DENV infection. Downregulation of IL-13 and MCP-3 was identified as a unique cytokine response profile of acute CHIKV infection, while distinct downregulation of PDGF-AB/BB and FGF-2 characterized the response from acute DENV infection. Our study provides an important overview of the host cytokine responses between CHIKV and DENV infection, which is important to further understand the mechanism and pathology of these diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06339-6.
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spelling pubmed-82542842021-07-06 Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection Dhenni, Rama Yohan, Benediktus Alisjahbana, Bachti Lucanus, Anton Riswari, Silvita Fitri Megawati, Dewi Haryanto, Sotianingsih Gampamole, Dekrit Hayati, Rahma F. Sari, Kartika Witari, Ni Putu Diah Myint, Khin Saw Aye Sasmono, R. Tedjo BMC Infect Dis Research Article BACKGROUND: Infection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated. Cytokines, which broadly also include chemokines and growth factors, have been shown to play a role in protective immunity as well as DENV and CHIKV pathogenesis. However, differences in cytokine response to both viruses remain poorly understood, especially in patients from countries where both viruses are endemic. Our study is therefore aimed to provide a comparative profiling of cytokine response induced by acute DENV and CHIKV infections in patients with similar disease stages and in experimental in vitro infections. METHODS: By using multiplex immunoassay, we compared host cytokine profiles between acute CHIKV and DENV infections by analysing serum cytokine levels of IL-1α, IL-4, IL-5, IL-8, IL-13, RANTES, MCP-3, eotaxin, PDGF-AB/BB, and FGF-2 from the sera of acute chikungunya and dengue fever patients. We further investigated the cytokine profile responses using experimental in vitro CHIKV and DENV infections of peripheral blood mononuclear cells (PBMCs). RESULTS: We found that both CHIKV and DENV-infected patients had an upregulated level of IL-8 and IL-4, with the highest IL-4 level observed in DENV-2 infected patients. Higher IL-8 level was also correlated with lower platelet count in dengue patients. IL-13 and MCP-3 downregulation was observed only in chikungunya patients, while conversely PDGF-AB/BB and FGF-2 downregulation was unique in dengue patients. Age-associated differential expression of IL-13, MCP-3, and IL-5 was also observed, while distinct kinetics of IL-4, IL-8, and FGF-2 expression between CHIKV and DENV-infected patients were identified. Furthermore, the unique pattern of IL-8, IL-13 and MCP-3, but not IL-4 expression was also recapitulated using experimental in vitro infection in PBMCs. CONCLUSIONS: Taken together, our study identified common cytokine response profile characterized by upregulation of IL-8 and IL-4 between CHIKV and DENV infection. Downregulation of IL-13 and MCP-3 was identified as a unique cytokine response profile of acute CHIKV infection, while distinct downregulation of PDGF-AB/BB and FGF-2 characterized the response from acute DENV infection. Our study provides an important overview of the host cytokine responses between CHIKV and DENV infection, which is important to further understand the mechanism and pathology of these diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06339-6. BioMed Central 2021-07-02 /pmc/articles/PMC8254284/ /pubmed/34215212 http://dx.doi.org/10.1186/s12879-021-06339-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Dhenni, Rama
Yohan, Benediktus
Alisjahbana, Bachti
Lucanus, Anton
Riswari, Silvita Fitri
Megawati, Dewi
Haryanto, Sotianingsih
Gampamole, Dekrit
Hayati, Rahma F.
Sari, Kartika
Witari, Ni Putu Diah
Myint, Khin Saw Aye
Sasmono, R. Tedjo
Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection
title Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection
title_full Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection
title_fullStr Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection
title_full_unstemmed Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection
title_short Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection
title_sort comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254284/
https://www.ncbi.nlm.nih.gov/pubmed/34215212
http://dx.doi.org/10.1186/s12879-021-06339-6
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