Cannabis smoke suppresses antiviral immune responses to influenza A in mice

Rationale Despite its increasingly widespread use, little is known about the impact of cannabis smoking on the response to viral infections like influenza A virus (IAV). Many assume that cannabis smoking will disrupt antiviral responses in a manner similar to cigarette smoking; however, since cannab...

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Main Authors: Nadia Milad, Matthew F. Fantauzzi, Joshua J.C. McGrath, Steven P. Cass, Danya Thayaparan, Peiyao Wang, Sam Afkhami, Jennifer A. Aguiar, Kjetil Ask, Andrew C. Doxey, Martin R. Stampfli, Jeremy A. Hirota
Format: Article
Language:English
Published: European Respiratory Society 2023-11-01
Series:ERJ Open Research
Online Access:http://openres.ersjournals.com/content/9/6/00219-2023.full
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author Nadia Milad
Matthew F. Fantauzzi
Joshua J.C. McGrath
Steven P. Cass
Danya Thayaparan
Peiyao Wang
Sam Afkhami
Jennifer A. Aguiar
Kjetil Ask
Andrew C. Doxey
Martin R. Stampfli
Jeremy A. Hirota
author_facet Nadia Milad
Matthew F. Fantauzzi
Joshua J.C. McGrath
Steven P. Cass
Danya Thayaparan
Peiyao Wang
Sam Afkhami
Jennifer A. Aguiar
Kjetil Ask
Andrew C. Doxey
Martin R. Stampfli
Jeremy A. Hirota
author_sort Nadia Milad
collection DOAJ
description Rationale Despite its increasingly widespread use, little is known about the impact of cannabis smoking on the response to viral infections like influenza A virus (IAV). Many assume that cannabis smoking will disrupt antiviral responses in a manner similar to cigarette smoking; however, since cannabinoids exhibit anti-inflammatory effects, cannabis smoke exposure may impact viral infection in distinct ways. Methods Male and female BALB/c mice were exposed daily to cannabis smoke and concurrently intranasally instilled with IAV. Viral burden, inflammatory mediator levels (multiplex ELISA), lung immune cells populations (flow cytometry) and gene expression patterns (RNA sequencing) were assessed in the lungs. Plasma IAV-specific antibodies were measured via ELISA. Results We found that cannabis smoke exposure increased pulmonary viral burden while decreasing total leukocytes, including macrophages, monocytes and dendritic cell populations in the lungs. Furthermore, infection-induced upregulation of certain inflammatory mediators (interferon-γ and C-C motif chemokine ligand 5) was blunted by cannabis smoke exposure, which in females was linked to the transcriptional downregulation of pathways involved in innate and adaptive immune responses. Finally, plasma levels of IAV-specific IgM and IgG1 were significantly decreased in cannabis smoke-exposed, infected mice compared to infected controls, only in female mice. Conclusions Overall, cannabis smoke exposure disrupted host-defence processes, leading to increased viral burden and dampened inflammatory signalling. These results suggest that cannabis smoking is detrimental to the maintenance of pulmonary homeostasis during viral infection and highlight the need for data regarding the impact on immune competency in humans.
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spelling doaj.art-701d31614b5d4540a65bf088276e3fa62024-01-08T09:57:43ZengEuropean Respiratory SocietyERJ Open Research2312-05412023-11-019610.1183/23120541.00219-202300219-2023Cannabis smoke suppresses antiviral immune responses to influenza A in miceNadia Milad0Matthew F. Fantauzzi1Joshua J.C. McGrath2Steven P. Cass3Danya Thayaparan4Peiyao Wang5Sam Afkhami6Jennifer A. Aguiar7Kjetil Ask8Andrew C. Doxey9Martin R. Stampfli10Jeremy A. Hirota11 Department of Medicine, McMaster University, Hamilton, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada Drukier Institute for Children's Health, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA Department of Medicine, McMaster University, Hamilton, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada Department of Biology, University of Waterloo, Waterloo, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada Department of Biology, University of Waterloo, Waterloo, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada Department of Medicine, McMaster University, Hamilton, ON, Canada Rationale Despite its increasingly widespread use, little is known about the impact of cannabis smoking on the response to viral infections like influenza A virus (IAV). Many assume that cannabis smoking will disrupt antiviral responses in a manner similar to cigarette smoking; however, since cannabinoids exhibit anti-inflammatory effects, cannabis smoke exposure may impact viral infection in distinct ways. Methods Male and female BALB/c mice were exposed daily to cannabis smoke and concurrently intranasally instilled with IAV. Viral burden, inflammatory mediator levels (multiplex ELISA), lung immune cells populations (flow cytometry) and gene expression patterns (RNA sequencing) were assessed in the lungs. Plasma IAV-specific antibodies were measured via ELISA. Results We found that cannabis smoke exposure increased pulmonary viral burden while decreasing total leukocytes, including macrophages, monocytes and dendritic cell populations in the lungs. Furthermore, infection-induced upregulation of certain inflammatory mediators (interferon-γ and C-C motif chemokine ligand 5) was blunted by cannabis smoke exposure, which in females was linked to the transcriptional downregulation of pathways involved in innate and adaptive immune responses. Finally, plasma levels of IAV-specific IgM and IgG1 were significantly decreased in cannabis smoke-exposed, infected mice compared to infected controls, only in female mice. Conclusions Overall, cannabis smoke exposure disrupted host-defence processes, leading to increased viral burden and dampened inflammatory signalling. These results suggest that cannabis smoking is detrimental to the maintenance of pulmonary homeostasis during viral infection and highlight the need for data regarding the impact on immune competency in humans.http://openres.ersjournals.com/content/9/6/00219-2023.full
spellingShingle Nadia Milad
Matthew F. Fantauzzi
Joshua J.C. McGrath
Steven P. Cass
Danya Thayaparan
Peiyao Wang
Sam Afkhami
Jennifer A. Aguiar
Kjetil Ask
Andrew C. Doxey
Martin R. Stampfli
Jeremy A. Hirota
Cannabis smoke suppresses antiviral immune responses to influenza A in mice
ERJ Open Research
title Cannabis smoke suppresses antiviral immune responses to influenza A in mice
title_full Cannabis smoke suppresses antiviral immune responses to influenza A in mice
title_fullStr Cannabis smoke suppresses antiviral immune responses to influenza A in mice
title_full_unstemmed Cannabis smoke suppresses antiviral immune responses to influenza A in mice
title_short Cannabis smoke suppresses antiviral immune responses to influenza A in mice
title_sort cannabis smoke suppresses antiviral immune responses to influenza a in mice
url http://openres.ersjournals.com/content/9/6/00219-2023.full
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