Neutrophil activation and early features of NET formation are associated with Dengue virus infection in human

The involvement of the immune system in the protection and pathology of natural dengue virus (DENV) has been extensively studied. However, despite studies that have referred to activation of neutrophils in DENV infections, the exact roles of neutrophils remain elusive. Here, we explored the phenotyp...

Full description

Bibliographic Details
Main Authors: Opasawatchai, A, Amornsupawat, P, Jiravejchakul, N, Chan-In, W, Spoerk, N, Manopwisedjaroen, K, Singhasivanon, P, Yingtaweesak, T, Suraamornkul, S, Mongkolsapaya, J, Sakuntabhai, A, Matangkasombut, P, Loison, F
Format: Journal article
Language:English
Published: Frontiers Media 2019
_version_ 1826265960148893696
author Opasawatchai, A
Amornsupawat, P
Jiravejchakul, N
Chan-In, W
Spoerk, N
Manopwisedjaroen, K
Singhasivanon, P
Yingtaweesak, T
Suraamornkul, S
Mongkolsapaya, J
Sakuntabhai, A
Matangkasombut, P
Loison, F
author_facet Opasawatchai, A
Amornsupawat, P
Jiravejchakul, N
Chan-In, W
Spoerk, N
Manopwisedjaroen, K
Singhasivanon, P
Yingtaweesak, T
Suraamornkul, S
Mongkolsapaya, J
Sakuntabhai, A
Matangkasombut, P
Loison, F
author_sort Opasawatchai, A
collection OXFORD
description The involvement of the immune system in the protection and pathology of natural dengue virus (DENV) has been extensively studied. However, despite studies that have referred to activation of neutrophils in DENV infections, the exact roles of neutrophils remain elusive. Here, we explored the phenotypic and functional responses of neutrophils in a cohort of adult dengue patients. Results indicated that during an acute DENV infection, neutrophils up-regulate CD66b expression, and produce a more robust respiratory response as compared with that in convalescent or healthy individuals; this confirmed in vivo neutrophil activation during DENV infection. Spontaneous decondensation of nuclei, an early event of neutrophil extracellular trap (NET) formation, was also markedly increased in cells isolated from DENV-infected patients during the acute phase of the infection. In vitro incubation of NETs with DENV-2 virus significantly decreased DENV infectivity. Interestingly, increased levels of NET components were found in the serum of patients with more severe disease form-dengue hemorrhagic fever (DHF), but not uncomplicated dengue fever, during the acute phase of the infection. Levels of pro-inflammatory cytokines IL-8 and TNFα were also increased in DHF patients as compared with those in healthy and DF subjects. This suggested that NETs may play dual roles during DENV infection. The increased ability for NET formation during acute DENV infection appeared to be independent of PAD4-mediated histone H3 hyper-citrullination. Our study suggests that neutrophils are involved in immunological responses to DENV infection.
first_indexed 2024-03-06T20:31:44Z
format Journal article
id oxford-uuid:314753a8-653e-4e80-9947-c194dcea7adc
institution University of Oxford
language English
last_indexed 2024-03-06T20:31:44Z
publishDate 2019
publisher Frontiers Media
record_format dspace
spelling oxford-uuid:314753a8-653e-4e80-9947-c194dcea7adc2022-03-26T13:06:54ZNeutrophil activation and early features of NET formation are associated with Dengue virus infection in humanJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:314753a8-653e-4e80-9947-c194dcea7adcEnglishSymplectic Elements at OxfordFrontiers Media2019Opasawatchai, AAmornsupawat, PJiravejchakul, NChan-In, WSpoerk, NManopwisedjaroen, KSinghasivanon, PYingtaweesak, TSuraamornkul, SMongkolsapaya, JSakuntabhai, AMatangkasombut, PLoison, FThe involvement of the immune system in the protection and pathology of natural dengue virus (DENV) has been extensively studied. However, despite studies that have referred to activation of neutrophils in DENV infections, the exact roles of neutrophils remain elusive. Here, we explored the phenotypic and functional responses of neutrophils in a cohort of adult dengue patients. Results indicated that during an acute DENV infection, neutrophils up-regulate CD66b expression, and produce a more robust respiratory response as compared with that in convalescent or healthy individuals; this confirmed in vivo neutrophil activation during DENV infection. Spontaneous decondensation of nuclei, an early event of neutrophil extracellular trap (NET) formation, was also markedly increased in cells isolated from DENV-infected patients during the acute phase of the infection. In vitro incubation of NETs with DENV-2 virus significantly decreased DENV infectivity. Interestingly, increased levels of NET components were found in the serum of patients with more severe disease form-dengue hemorrhagic fever (DHF), but not uncomplicated dengue fever, during the acute phase of the infection. Levels of pro-inflammatory cytokines IL-8 and TNFα were also increased in DHF patients as compared with those in healthy and DF subjects. This suggested that NETs may play dual roles during DENV infection. The increased ability for NET formation during acute DENV infection appeared to be independent of PAD4-mediated histone H3 hyper-citrullination. Our study suggests that neutrophils are involved in immunological responses to DENV infection.
spellingShingle Opasawatchai, A
Amornsupawat, P
Jiravejchakul, N
Chan-In, W
Spoerk, N
Manopwisedjaroen, K
Singhasivanon, P
Yingtaweesak, T
Suraamornkul, S
Mongkolsapaya, J
Sakuntabhai, A
Matangkasombut, P
Loison, F
Neutrophil activation and early features of NET formation are associated with Dengue virus infection in human
title Neutrophil activation and early features of NET formation are associated with Dengue virus infection in human
title_full Neutrophil activation and early features of NET formation are associated with Dengue virus infection in human
title_fullStr Neutrophil activation and early features of NET formation are associated with Dengue virus infection in human
title_full_unstemmed Neutrophil activation and early features of NET formation are associated with Dengue virus infection in human
title_short Neutrophil activation and early features of NET formation are associated with Dengue virus infection in human
title_sort neutrophil activation and early features of net formation are associated with dengue virus infection in human
work_keys_str_mv AT opasawatchaia neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT amornsupawatp neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT jiravejchakuln neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT chaninw neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT spoerkn neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT manopwisedjaroenk neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT singhasivanonp neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT yingtaweesakt neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT suraamornkuls neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT mongkolsapayaj neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT sakuntabhaia neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT matangkasombutp neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman
AT loisonf neutrophilactivationandearlyfeaturesofnetformationareassociatedwithdenguevirusinfectioninhuman