Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Autores
Habibi, Maximillian S.; Thwaites, Ryan S.; Chang, Meiping; Jozwik, Agnieszka; Paras, Allan; Kirsebom, Freja; Varese, Augusto; Owen, Amber; Cuthbertson, Leah; James, Phillip; Tunstall, Tanushree; Nickle, David; Hansel, Trevor T.; Moffatt, Miriam F.; Johansson, Cecilia; Chiu, Christopher; Openshaw, Peter J. M.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.
Fil: Habibi, Maximillian S.. Imperial College London; Reino Unido
Fil: Thwaites, Ryan S.. Imperial College London; Reino Unido
Fil: Chang, Meiping. No especifíca;
Fil: Jozwik, Agnieszka. Imperial College London; Reino Unido
Fil: Paras, Allan. Imperial College London; Reino Unido
Fil: Kirsebom, Freja. Imperial College London; Reino Unido
Fil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Owen, Amber. Imperial College London; Reino Unido
Fil: Cuthbertson, Leah. Imperial College London; Reino Unido
Fil: James, Phillip. Imperial College London; Reino Unido
Fil: Tunstall, Tanushree. Imperial College London; Reino Unido
Fil: Nickle, David. No especifíca;
Fil: Hansel, Trevor T.. Imperial College London; Reino Unido
Fil: Moffatt, Miriam F.. Imperial College London; Reino Unido
Fil: Johansson, Cecilia. Imperial College London; Reino Unido
Fil: Chiu, Christopher. Imperial College London; Reino Unido
Fil: Openshaw, Peter J. M.. Imperial College London; Reino Unido
Materia
NEUTROPHIL
RESPIRATORY SYNCITIAL VIRUS
RESPIRATORY MUCOSA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/217179
Acceder
id CONICETDig_0b15ae801c34aa27e2e701b16986271a
oai_identifier_str oai:ri.conicet.gov.ar:11336/217179
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infectionHabibi, Maximillian S.Thwaites, Ryan S.Chang, MeipingJozwik, AgnieszkaParas, AllanKirsebom, FrejaVarese, AugustoOwen, AmberCuthbertson, LeahJames, PhillipTunstall, TanushreeNickle, DavidHansel, Trevor T.Moffatt, Miriam F.Johansson, CeciliaChiu, ChristopherOpenshaw, Peter J. M.NEUTROPHILRESPIRATORY SYNCITIAL VIRUSRESPIRATORY MUCOSAhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.Fil: Habibi, Maximillian S.. Imperial College London; Reino UnidoFil: Thwaites, Ryan S.. Imperial College London; Reino UnidoFil: Chang, Meiping. No especifíca;Fil: Jozwik, Agnieszka. Imperial College London; Reino UnidoFil: Paras, Allan. Imperial College London; Reino UnidoFil: Kirsebom, Freja. Imperial College London; Reino UnidoFil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Owen, Amber. Imperial College London; Reino UnidoFil: Cuthbertson, Leah. Imperial College London; Reino UnidoFil: James, Phillip. Imperial College London; Reino UnidoFil: Tunstall, Tanushree. Imperial College London; Reino UnidoFil: Nickle, David. No especifíca;Fil: Hansel, Trevor T.. Imperial College London; Reino UnidoFil: Moffatt, Miriam F.. Imperial College London; Reino UnidoFil: Johansson, Cecilia. Imperial College London; Reino UnidoFil: Chiu, Christopher. Imperial College London; Reino UnidoFil: Openshaw, Peter J. M.. Imperial College London; Reino UnidoAmerican Association for the Advancement of Science2020-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/217179Habibi, Maximillian S.; Thwaites, Ryan S.; Chang, Meiping; Jozwik, Agnieszka; Paras, Allan; et al.; Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection; American Association for the Advancement of Science; Science; 370; 6513; 10-2020; 1-150036-8075CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1126/science.aba9301info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:20:48Zoai:ri.conicet.gov.ar:11336/217179instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:20:48.833CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
title Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
spellingShingle Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
Habibi, Maximillian S.
NEUTROPHIL
RESPIRATORY SYNCITIAL VIRUS
RESPIRATORY MUCOSA
title_short Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
title_full Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
title_fullStr Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
title_full_unstemmed Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
title_sort Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
dc.creator.none.fl_str_mv Habibi, Maximillian S.
Thwaites, Ryan S.
Chang, Meiping
Jozwik, Agnieszka
Paras, Allan
Kirsebom, Freja
Varese, Augusto
Owen, Amber
Cuthbertson, Leah
James, Phillip
Tunstall, Tanushree
Nickle, David
Hansel, Trevor T.
Moffatt, Miriam F.
Johansson, Cecilia
Chiu, Christopher
Openshaw, Peter J. M.
author Habibi, Maximillian S.
author_facet Habibi, Maximillian S.
Thwaites, Ryan S.
Chang, Meiping
Jozwik, Agnieszka
Paras, Allan
Kirsebom, Freja
Varese, Augusto
Owen, Amber
Cuthbertson, Leah
James, Phillip
Tunstall, Tanushree
Nickle, David
Hansel, Trevor T.
Moffatt, Miriam F.
Johansson, Cecilia
Chiu, Christopher
Openshaw, Peter J. M.
author_role author
author2 Thwaites, Ryan S.
Chang, Meiping
Jozwik, Agnieszka
Paras, Allan
Kirsebom, Freja
Varese, Augusto
Owen, Amber
Cuthbertson, Leah
James, Phillip
Tunstall, Tanushree
Nickle, David
Hansel, Trevor T.
Moffatt, Miriam F.
Johansson, Cecilia
Chiu, Christopher
Openshaw, Peter J. M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NEUTROPHIL
RESPIRATORY SYNCITIAL VIRUS
RESPIRATORY MUCOSA
topic NEUTROPHIL
RESPIRATORY SYNCITIAL VIRUS
RESPIRATORY MUCOSA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.
Fil: Habibi, Maximillian S.. Imperial College London; Reino Unido
Fil: Thwaites, Ryan S.. Imperial College London; Reino Unido
Fil: Chang, Meiping. No especifíca;
Fil: Jozwik, Agnieszka. Imperial College London; Reino Unido
Fil: Paras, Allan. Imperial College London; Reino Unido
Fil: Kirsebom, Freja. Imperial College London; Reino Unido
Fil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Owen, Amber. Imperial College London; Reino Unido
Fil: Cuthbertson, Leah. Imperial College London; Reino Unido
Fil: James, Phillip. Imperial College London; Reino Unido
Fil: Tunstall, Tanushree. Imperial College London; Reino Unido
Fil: Nickle, David. No especifíca;
Fil: Hansel, Trevor T.. Imperial College London; Reino Unido
Fil: Moffatt, Miriam F.. Imperial College London; Reino Unido
Fil: Johansson, Cecilia. Imperial College London; Reino Unido
Fil: Chiu, Christopher. Imperial College London; Reino Unido
Fil: Openshaw, Peter J. M.. Imperial College London; Reino Unido
description The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/217179
Habibi, Maximillian S.; Thwaites, Ryan S.; Chang, Meiping; Jozwik, Agnieszka; Paras, Allan; et al.; Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection; American Association for the Advancement of Science; Science; 370; 6513; 10-2020; 1-15
0036-8075
CONICET Digital
CONICET
url http://hdl.handle.net/11336/217179
identifier_str_mv Habibi, Maximillian S.; Thwaites, Ryan S.; Chang, Meiping; Jozwik, Agnieszka; Paras, Allan; et al.; Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection; American Association for the Advancement of Science; Science; 370; 6513; 10-2020; 1-15
0036-8075
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1126/science.aba9301
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846781703535722496
score 12.982451

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