Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations

Orestis Katsoulis; Marie Toussaint; Millie M. Jackson; Patrick Mallia; Joseph Footitt; Kyle T. Mincham; Garance F.M. Meyer; Tata Kebadze; Amy Gilmour; Merete Long; Andrew D. Aswani; Robert J. Snelgrove; Sebastian L. Johnston; James D. Chalmers; Aran Singanayagam

doi:10.1038/s41467-024-50197-0

Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations

Orestis Katsoulis
, Marie Toussaint
, Millie M. Jackson
, Patrick Mallia
, Joseph Footitt
, Kyle T. Mincham
, Garance F.M. Meyer
, Tata Kebadze
, Amy Gilmour
, Merete Long
, Andrew D. Aswani
, Robert J. Snelgrove
, Sebastian L. Johnston
, James D. Chalmers
, Aran Singanayagam (Lead / Corresponding author)

Respiratory Medicine and Gastroenterology

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

221 Downloads (Pure)

Abstract

Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.

Original language	English
Article number	5766
Number of pages	14
Journal	Nature Communications
Volume	15
DOIs	https://doi.org/10.1038/s41467-024-50197-0
Publication status	Published - 9 Jul 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-024-50197-0Licence: CC BY

Final Published VersionFinal published version, 3.08 MBLicence: CC BY

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Katsoulis, O., Toussaint, M., Jackson, M. M., Mallia, P., Footitt, J., Mincham, K. T., Meyer, G. F. M., Kebadze, T., Gilmour, A., Long, M., Aswani, A. D., Snelgrove, R. J., Johnston, S. L., Chalmers, J. D., & Singanayagam, A. (2024). Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations. Nature Communications, 15, Article 5766. https://doi.org/10.1038/s41467-024-50197-0

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title = "Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations",

abstract = "Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.",

author = "Orestis Katsoulis and Marie Toussaint and Jackson, \{Millie M.\} and Patrick Mallia and Joseph Footitt and Mincham, \{Kyle T.\} and Meyer, \{Garance F.M.\} and Tata Kebadze and Amy Gilmour and Merete Long and Aswani, \{Andrew D.\} and Snelgrove, \{Robert J.\} and Johnston, \{Sebastian L.\} and Chalmers, \{James D.\} and Aran Singanayagam",

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doi = "10.1038/s41467-024-50197-0",

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Katsoulis, O, Toussaint, M, Jackson, MM, Mallia, P, Footitt, J, Mincham, KT, Meyer, GFM, Kebadze, T, Gilmour, A , Long, M, Aswani, AD, Snelgrove, RJ, Johnston, SL, Chalmers, JD & Singanayagam, A 2024, 'Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations', Nature Communications, vol. 15, 5766. https://doi.org/10.1038/s41467-024-50197-0

TY - JOUR

T1 - Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations

AU - Katsoulis, Orestis

AU - Toussaint, Marie

AU - Jackson, Millie M.

AU - Mallia, Patrick

AU - Footitt, Joseph

AU - Mincham, Kyle T.

AU - Meyer, Garance F.M.

AU - Kebadze, Tata

AU - Gilmour, Amy

AU - Long, Merete

AU - Aswani, Andrew D.

AU - Snelgrove, Robert J.

AU - Johnston, Sebastian L.

AU - Chalmers, James D.

AU - Singanayagam, Aran

PY - 2024/7/9

Y1 - 2024/7/9

N2 - Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.

AB - Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.

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DO - 10.1038/s41467-024-50197-0

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SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

M1 - 5766

ER -

Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations

Abstract

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