Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier

Functional neutrophil diversity is recognized as a driver of development, progression and resolution of disease. Recruited neutrophils are imprinted by biochemical, biophysical and mechanical stimuli of the encountered microenvironment, altering their genetic and phenotypic program. The functional i...

Descripción completa

Detalles Bibliográficos
Autores: Singh, Ashish K., O'Mara, Maurice, Drieu La Rochelle, Julie, Therry, Noemie, D'Alessio, Aurora, Baugh, John, Barre, Ramya S., Matsumoto, Misaki, Nogales, Aitor, Martínez-Sobrido, Luis, Knaus, Ulla G.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/416340
Acceso en línea:http://hdl.handle.net/10261/416340
https://api.elsevier.com/content/abstract/scopus_id/105019934178
Access Level:acceso abierto
Palabra clave:Inflammatory Bowel Disease (IBD)
Influenza A virus
NADPH oxidase
Neutrophils
Pulmonary disease
Staphylococcus aureus
id ES_1793390e97f1db8cee2d2c42dd4a19bc
oai_identifier_str oai:digital.csic.es:10261/416340
network_acronym_str ES
network_name_str España
repository_id_str
spelling Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrierSingh, Ashish K.O'Mara, MauriceDrieu La Rochelle, JulieTherry, NoemieD'Alessio, AuroraBaugh, JohnBarre, Ramya S.Matsumoto, MisakiNogales, AitorMartínez-Sobrido, LuisKnaus, Ulla G.Inflammatory Bowel Disease (IBD)Influenza A virusNADPH oxidaseNeutrophilsPulmonary diseaseStaphylococcus aureusFunctional neutrophil diversity is recognized as a driver of development, progression and resolution of disease. Recruited neutrophils are imprinted by biochemical, biophysical and mechanical stimuli of the encountered microenvironment, altering their genetic and phenotypic program. The functional implications of this reprogramming are of critical importance for devising strategies to modify neutrophil behavior. Oxidant production affects neutrophil responses, shapes the microenvironment and often determines disease outcome in inflammation, infection and cancer. Here we report neutrophil diversification at mucosal barriers in inflammatory and infectious disease, culminating in tissue and stimulus-dependent de novo expression of the NADPH oxidases NOX1, DUOX2, and DUOX1 in recruited neutrophils. In contrast to proinflammatory DUOX2, myeloid NOX1 ameliorated colonic inflammation, yet epithelial NOX1 increased neutrophil recruitment from the onset, with a similar response observed in pulmonary S. aureus infection. In contrast, neutrophil DUOX expression did not alter S. aureus disease progression but extended host survival in influenza A virus infection. Thus, at gut and lung barriers an expansion of neutrophil oxidases occurs that highlights proinflammatory and antimicrobial DUOX2 activity, while NOX1 function seems intricate with multiple inputs. Evaluation of these de novo expressed oxidases in other neutrophil-driven diseases will further uncover their contribution to host protection and pathogenesis.We thank the staff of the Biomedical Facility, Flow Cytometry Core Facility, and Josie Ward for their technical support. We also thank Rachel McLoughlin, Seamus Hussey, Christa Zerbe, Stephen Lalor, Carsten Kroger, and James Doroshow for providing reagents and Children's Health Foundation Ireland for the DOCHAS repository. This study was supported by Health Research Board Ireland ILP-POR-2022-018, Science Foundation Ireland 16/IA/4501 and 22/FFP-A/10349 (all UGK).Peer reviewedElsevierScience Foundation IrelandKnaus, Ulla G. [0000-0002-7375-0385]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/416340https://api.elsevier.com/content/abstract/scopus_id/105019934178reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.redox.2025.103883https://doi.org/10.1016/j.redox.2025.103883Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4163402026-05-22T06:33:51Z
dc.title.none.fl_str_mv Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
title Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
spellingShingle Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
Singh, Ashish K.
Inflammatory Bowel Disease (IBD)
Influenza A virus
NADPH oxidase
Neutrophils
Pulmonary disease
Staphylococcus aureus
title_short Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
title_full Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
title_fullStr Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
title_full_unstemmed Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
title_sort Emergence of NOX1/DUOX NADPH oxidases is a key feature of functional neutrophil reprogramming at the gut and lung barrier
dc.creator.none.fl_str_mv Singh, Ashish K.
O'Mara, Maurice
Drieu La Rochelle, Julie
Therry, Noemie
D'Alessio, Aurora
Baugh, John
Barre, Ramya S.
Matsumoto, Misaki
Nogales, Aitor
Martínez-Sobrido, Luis
Knaus, Ulla G.
author Singh, Ashish K.
author_facet Singh, Ashish K.
O'Mara, Maurice
Drieu La Rochelle, Julie
Therry, Noemie
D'Alessio, Aurora
Baugh, John
Barre, Ramya S.
Matsumoto, Misaki
Nogales, Aitor
Martínez-Sobrido, Luis
Knaus, Ulla G.
author_role author
author2 O'Mara, Maurice
Drieu La Rochelle, Julie
Therry, Noemie
D'Alessio, Aurora
Baugh, John
Barre, Ramya S.
Matsumoto, Misaki
Nogales, Aitor
Martínez-Sobrido, Luis
Knaus, Ulla G.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Science Foundation Ireland
Knaus, Ulla G. [0000-0002-7375-0385]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Inflammatory Bowel Disease (IBD)
Influenza A virus
NADPH oxidase
Neutrophils
Pulmonary disease
Staphylococcus aureus
topic Inflammatory Bowel Disease (IBD)
Influenza A virus
NADPH oxidase
Neutrophils
Pulmonary disease
Staphylococcus aureus
description Functional neutrophil diversity is recognized as a driver of development, progression and resolution of disease. Recruited neutrophils are imprinted by biochemical, biophysical and mechanical stimuli of the encountered microenvironment, altering their genetic and phenotypic program. The functional implications of this reprogramming are of critical importance for devising strategies to modify neutrophil behavior. Oxidant production affects neutrophil responses, shapes the microenvironment and often determines disease outcome in inflammation, infection and cancer. Here we report neutrophil diversification at mucosal barriers in inflammatory and infectious disease, culminating in tissue and stimulus-dependent de novo expression of the NADPH oxidases NOX1, DUOX2, and DUOX1 in recruited neutrophils. In contrast to proinflammatory DUOX2, myeloid NOX1 ameliorated colonic inflammation, yet epithelial NOX1 increased neutrophil recruitment from the onset, with a similar response observed in pulmonary S. aureus infection. In contrast, neutrophil DUOX expression did not alter S. aureus disease progression but extended host survival in influenza A virus infection. Thus, at gut and lung barriers an expansion of neutrophil oxidases occurs that highlights proinflammatory and antimicrobial DUOX2 activity, while NOX1 function seems intricate with multiple inputs. Evaluation of these de novo expressed oxidases in other neutrophil-driven diseases will further uncover their contribution to host protection and pathogenesis.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/416340
https://api.elsevier.com/content/abstract/scopus_id/105019934178
url http://hdl.handle.net/10261/416340
https://api.elsevier.com/content/abstract/scopus_id/105019934178
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.redox.2025.103883
https://doi.org/10.1016/j.redox.2025.103883
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869403930518093824
score 15.812429

Similares en LA Referencia