Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions

Cigarette smoke augments CSF3 expression in neutrophils to compromise alveolar-capillary barrier function during influenza infection

Joshua J.C. McGrath, Gilles Vanderstocken, Anna Dvorkin-Gheva, Steven P. Cass, Sam Afkhami, Matthew F. Fantauzzi, Danya Thayaparan, Amir Reihani, Peiyao Wang, Ashley Beaulieu, Pamela Shen, Mathieu Morissette, Rodrigo Jiménez-Saiz, Spencer D. Revill, Arata Tabuchi, Diana Zabini, Warren L. Lee, Carl D. Richards, Matthew S. Miller, Kjetil Ask, Wolfgang M. Kuebler, Jeremy A. Simpson, Martin R. Stämpfli
European Respiratory Journal 2022; DOI: 10.1183/13993003.02049-2021
Joshua J.C. McGrath
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
15Authors contributed equally
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Joshua J.C. McGrath
Gilles Vanderstocken
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
15Authors contributed equally
17Current Address: GV: Enzybel International SA, Route de Lennik, 802-1070 Brussels, Belgium
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Dvorkin-Gheva
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anna Dvorkin-Gheva
Steven P. Cass
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Steven P. Cass
Sam Afkhami
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew F. Fantauzzi
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Danya Thayaparan
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amir Reihani
3Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
4The Research Institute of St. Joe's Hamilton, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peiyao Wang
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ashley Beaulieu
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pamela Shen
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
18Current Address: PS: Merck & Co., Inc., West Point, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mathieu Morissette
5Department of Medicine, Université Laval, Quebec City, QC, Canada
6Quebec Heart and Lung Institute, Université Laval, Quebec City, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rodrigo Jiménez-Saiz
2Department of Medicine, McMaster University, Hamilton, ON, Canada
7Department of Immunology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa, Madrid, Spain
8Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain
9Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rodrigo Jiménez-Saiz
Spencer D. Revill
3Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
4The Research Institute of St. Joe's Hamilton, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arata Tabuchi
10Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Diana Zabini
10Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Warren L. Lee
10Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carl D. Richards
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew S. Miller
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
11Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
12Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kjetil Ask
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
3Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kjetil Ask
Wolfgang M. Kuebler
10Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada
13Institute of Physiology, Charité Universitätsmedizin Berlin, Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremy A. Simpson
14Dept. of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin R. Stämpfli
1McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
2Department of Medicine, McMaster University, Hamilton, ON, Canada
3Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada
16Current Address: MRS: CSL Biologics Research Center, Freiburgstrasse 3, CH-3010 Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: stampfli@mcmaster.ca
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

Background Cigarette smokers are at increased risk of acquiring influenza, developing severe disease, and requiring hospitalization/ICU admission following infection. However, immune mechanisms underlying this predisposition are incompletely understood, and therapeutic strategies for influenza are limited.

Methods We used a mouse model of concurrent cigarette smoke exposure and H1N1 influenza infection, colony-stimulating factor (CSF)3 supplementation/receptor (CSF3R) blockade, and single-cell RNA sequencing (scRNAseq) to investigate this relationship.

Results Cigarette smoke exposure exacerbated features of viral pneumonia such as edema, hypoxemia, and pulmonary neutrophilia. Smoke-exposed, infected mice demonstrated an increase in viral (v)RNA, but not replication-competent viral particles, relative to infection-only controls. Interstitial rather than airspace neutrophilia positively predicted morbidity in smoke-exposed, infected mice. Screening of pulmonary cytokines using a novel dysregulation score identified an exacerbated expression of CSF3 and interleukin (IL)-6 in the context of smoke exposure and influenza. Recombinant (r)CSF3 supplementation during influenza aggravated morbidity, hypothermia, and edema, while anti-CSF3R treatment of smoke-exposed infected mice improved alveolar-capillary barrier function. scRNAseq delineated a shift in the distribution of Csf3+ cells towards neutrophils in the context of cigarette smoke and influenza. However, although smoke-exposed lungs were enriched for infected, highly-activated neutrophils, gene signatures of these cells largely reflected an exacerbated form of typical influenza with select unique regulatory features.

Conclusion This work provides novel insight into the mechanisms by which cigarette smoke exacerbates influenza infection, unveiling potential therapeutic targets (e.g. excess vRNA accumulation, edematous CSF3R signaling) for use in this context, and potential limitations for clinical rCSF3 therapy during viral infectious disease.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Miller reports consulting fees for scientific advisory board participation from Seqirus and Medicago (influenza vaccines); lecture honoraria for lunch-and-learn on COVID-19 vaccines from Boehringer-Ingelheim; outside the submitted work.

Conflict of interest: Ask reports grants from Alkermes, Prometic, GSK, Canadian Institute for Health Research, Pharmaxis, Indalo, Unity Biotechnology, Canadian Pulmonary Fibrosis Association, Collaborative Health Research Projects, Pieris Pharmaceuticals, Bold Therapeutics, Pliant, CSL Behring, Boehringer Ingelheim; lecture honoraria from Boehringer Ingelheim; travel support from Boehringer Ingelheim; outside the submitted work.

Conflict of interest: Kuebler reports grant-in-aid from Canadian Institutes of Health Research (CIHR), during the course of the present study; grants-in-aid from German Research Foundation (DFG), German Ministry for Research and Education (BMBF), Berlin Institute of Health (BIH), German Centre for Cardiovascular Research (DZHK); outside the submitted work.

Conflict of interest: Stampfli reports support for the present manuscript from Canadian Institutes of Health Research; grants from RespiVert Pharmaceuticals, Canadian Heart and Stroke Foundation, Ontario Thoracic Society; consulting fees from Boehringer Ingelheim; lecture honoraria from AstraZeneca; MTA for monoclonal antibody to block G-CSF from CSL Behring and is employed with CSL Behring since January 2020; outside the submitted work.

Conflict of interest: Dr. McGrath has nothing to disclose.

Conflict of interest: Dr. Vanderstocken has nothing to disclose.

Conflict of interest: Dr. Dvorkin-Gheva has nothing to disclose.

Conflict of interest: Dr. Cass has nothing to disclose.

Conflict of interest: Dr. Afkhami has nothing to disclose.

Conflict of interest: Dr. Fantauzzi has nothing to disclose.

Conflict of interest: Dr. Thayaparan has nothing to disclose.

Conflict of interest: Dr. Reihani has nothing to disclose.

Conflict of interest: Dr. Wang has nothing to disclose.

Conflict of interest: Dr. Beaulieu has nothing to disclose.

Conflict of interest: Dr. Shen has nothing to disclose.

Conflict of interest: Dr. Morissette has nothing to disclose.

Conflict of interest: Dr. Jiménez-Saiz has nothing to disclose.

Conflict of interest: Dr. Revill has nothing to disclose.

Conflict of interest: Dr. Tabuchi has nothing to disclose.

Conflict of interest: Dr. Zabini has nothing to disclose.

Conflict of interest: Dr. Lee has nothing to disclose.

Conflict of interest: Dr. Richards has nothing to disclose.

Conflict of interest: Dr. Simpson has nothing to disclose.

  • Received July 22, 2021.
  • Accepted December 29, 2021.
  • Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
View Full Text

ERS Members

myERS - ERS members : log in with your myERS username and password.

INDIVIDUALS

Log in Login as an individual user.

Forgot your username or password?

LIBRARY USERS

Log in through your institution

If your library has a subscription, you may already be logged in via your IP address. Otherwise you may be able to log in via one of the following routes.
You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.
If you think you should have access, please contact your librarian or email journals@ersnet.org

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top
View this article with LENS
Vol 59 Issue 5 Table of Contents
European Respiratory Journal: 59 (5)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Cigarette smoke augments CSF3 expression in neutrophils to compromise alveolar-capillary barrier function during influenza infection
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Cigarette smoke augments CSF3 expression in neutrophils to compromise alveolar-capillary barrier function during influenza infection
Joshua J.C. McGrath, Gilles Vanderstocken, Anna Dvorkin-Gheva, Steven P. Cass, Sam Afkhami, Matthew F. Fantauzzi, Danya Thayaparan, Amir Reihani, Peiyao Wang, Ashley Beaulieu, Pamela Shen, Mathieu Morissette, Rodrigo Jiménez-Saiz, Spencer D. Revill, Arata Tabuchi, Diana Zabini, Warren L. Lee, Carl D. Richards, Matthew S. Miller, Kjetil Ask, Wolfgang M. Kuebler, Jeremy A. Simpson, Martin R. Stämpfli
European Respiratory Journal Jan 2022, 2102049; DOI: 10.1183/13993003.02049-2021

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Cigarette smoke augments CSF3 expression in neutrophils to compromise alveolar-capillary barrier function during influenza infection
Joshua J.C. McGrath, Gilles Vanderstocken, Anna Dvorkin-Gheva, Steven P. Cass, Sam Afkhami, Matthew F. Fantauzzi, Danya Thayaparan, Amir Reihani, Peiyao Wang, Ashley Beaulieu, Pamela Shen, Mathieu Morissette, Rodrigo Jiménez-Saiz, Spencer D. Revill, Arata Tabuchi, Diana Zabini, Warren L. Lee, Carl D. Richards, Matthew S. Miller, Kjetil Ask, Wolfgang M. Kuebler, Jeremy A. Simpson, Martin R. Stämpfli
European Respiratory Journal Jan 2022, 2102049; DOI: 10.1183/13993003.02049-2021
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Cardiovascular outcomes in patients with chronic kidney disease and COVID-19: a multi-regional data-linkage study
  • Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey
  • Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children
Show more Original research article

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Reviewers
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2022 by the European Respiratory Society