Suppression of virus specific immune responses by IL-10 in acute dengue infection

BACKGROUND: Elevated IL-10 has been shown to be associated with severe dengue infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI. MATERIALS AND METHODS: Ex vivo and cultured IFNγ ELISpot assays for dengue virus (DENV) NS3 protein and non dengue viral protei...

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Main Authors: Malavige, G, Jeewandara, C, Alles, K, Salimi, M, Gomes, L, Kamaladasa, A, Jayaratne, S, Ogg, G
Format: Journal article
Language:English
Published: Public Library of Science 2013
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author Malavige, G
Jeewandara, C
Alles, K
Salimi, M
Gomes, L
Kamaladasa, A
Jayaratne, S
Ogg, G
author_facet Malavige, G
Jeewandara, C
Alles, K
Salimi, M
Gomes, L
Kamaladasa, A
Jayaratne, S
Ogg, G
author_sort Malavige, G
collection OXFORD
description BACKGROUND: Elevated IL-10 has been shown to be associated with severe dengue infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI. MATERIALS AND METHODS: Ex vivo and cultured IFNγ ELISpot assays for dengue virus (DENV) NS3 protein and non dengue viral proteins were carried out in 26 patients with acute DI (16 with dengue haemorrhagic fever) and 12 healthy dengue seropositive individuals from Sri Lanka. DENV serotype specific (SS) responses were determined by using a panel of SS peptides. RESULTS: Serum IL-10 level were significantly higher (p = 0.02) in those who did not have in vitro responses to DENV-SS peptides (mean 144.2 pg/ml) when compared to those who responded (mean 75.7 pg/ml). DENV-NS3 specific ex vivo IFNγ ELISpot responses were also significantly lower (p = 0.0001) in those who did not respond to DENV-SS peptides (mean 42 SFU/million PBMCs) when compared to those who responded to DENV-SS peptides (mean 1024 SFU/million PBMCs). Serum IL-10 levels correlated significantly (p = 0.03) and inversely (Spearmans R = -0.45) with ex vivo DENV-NS3 specific responses but not with ex vivo non DENV specific responses (Spearmans R = -014, p = 0.52). Blockage of IL-10 in vitro significantly increased (p = 0.04) the ex vivo IFNγ ELISpot DENV-NS3 specific responses but had no effect on responses to non DENV proteins. CONCLUSION: IL-10 appears to contribute to the pathogenesis of acute dengue infections by inhibiting DENV-specific T cell responses, which can be restored by blocking IL-10.
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spelling oxford-uuid:ae58ad8d-cdce-4b26-b68a-b8870a42c57c2022-03-27T03:41:50ZSuppression of virus specific immune responses by IL-10 in acute dengue infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ae58ad8d-cdce-4b26-b68a-b8870a42c57cEnglishSymplectic Elements at OxfordPublic Library of Science2013Malavige, GJeewandara, CAlles, KSalimi, MGomes, LKamaladasa, AJayaratne, SOgg, GBACKGROUND: Elevated IL-10 has been shown to be associated with severe dengue infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI. MATERIALS AND METHODS: Ex vivo and cultured IFNγ ELISpot assays for dengue virus (DENV) NS3 protein and non dengue viral proteins were carried out in 26 patients with acute DI (16 with dengue haemorrhagic fever) and 12 healthy dengue seropositive individuals from Sri Lanka. DENV serotype specific (SS) responses were determined by using a panel of SS peptides. RESULTS: Serum IL-10 level were significantly higher (p = 0.02) in those who did not have in vitro responses to DENV-SS peptides (mean 144.2 pg/ml) when compared to those who responded (mean 75.7 pg/ml). DENV-NS3 specific ex vivo IFNγ ELISpot responses were also significantly lower (p = 0.0001) in those who did not respond to DENV-SS peptides (mean 42 SFU/million PBMCs) when compared to those who responded to DENV-SS peptides (mean 1024 SFU/million PBMCs). Serum IL-10 levels correlated significantly (p = 0.03) and inversely (Spearmans R = -0.45) with ex vivo DENV-NS3 specific responses but not with ex vivo non DENV specific responses (Spearmans R = -014, p = 0.52). Blockage of IL-10 in vitro significantly increased (p = 0.04) the ex vivo IFNγ ELISpot DENV-NS3 specific responses but had no effect on responses to non DENV proteins. CONCLUSION: IL-10 appears to contribute to the pathogenesis of acute dengue infections by inhibiting DENV-specific T cell responses, which can be restored by blocking IL-10.
spellingShingle Malavige, G
Jeewandara, C
Alles, K
Salimi, M
Gomes, L
Kamaladasa, A
Jayaratne, S
Ogg, G
Suppression of virus specific immune responses by IL-10 in acute dengue infection
title Suppression of virus specific immune responses by IL-10 in acute dengue infection
title_full Suppression of virus specific immune responses by IL-10 in acute dengue infection
title_fullStr Suppression of virus specific immune responses by IL-10 in acute dengue infection
title_full_unstemmed Suppression of virus specific immune responses by IL-10 in acute dengue infection
title_short Suppression of virus specific immune responses by IL-10 in acute dengue infection
title_sort suppression of virus specific immune responses by il 10 in acute dengue infection
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