Infected wound repair correlates with collagen I induction and NOX2 activation by cold atmospheric plasma
Cold atmospheric plasma (CAP) is a promising complement to tissue repair and regenerative medicine approaches. CAP has therapeutic potential in infected cutaneous wounds by mechanisms which remain enigmatic. Here, CAP is shown to activate phagocyte NADPH oxidase complex NOX2. CAP induced increased intracellular reactive oxygen species, alleviated by NOX2 inhibitors. Genetic and pharmacological inhibitions of NOX2 in macrophages and bioengineered skin infected with Staphylococcus aureus and treated with CAP reduced intracellular oxidants and increased bacterial survival. CAP triggered Rac activation and phosphorylation of p40<sup>phox</sup> and p47<sup>phox</sup> required for NOX2 assembly and activity. Furthermore, CAP induced collagen I expression by fibroblasts. Infection and healing kinetics showed that murine skin wounds infected with S. aureus and treated with CAP are characterized by decreased bacterial burden, increased length of neoepidermis and extracellular matrix formation. Collectively, our findings identify mechanisms triggered by CAP that subdue infection and result in enhanced repair following skin injury.
Authors
- Antoine Rousseau (ORCID: https://orcid.org/0000-0002-8965-5307)
- Javier Pizarro‐Cerdá
- Julien Fernandes (ORCID: https://orcid.org/0000-0001-8768-625X)
- Elena Capuzzo (ORCID: https://orcid.org/0009-0001-3204-1208)
- Jean‐Jacques Lataillade (ORCID: https://orcid.org/0000-0002-4594-2398)
- Constance Duchesne
- Mélanie Hamon (ORCID: https://orcid.org/0000-0001-5078-4083)
- Nadira Frescaline (ORCID: https://orcid.org/0000-0002-2673-8025)
- Océane Blaise
- Sébastien Banzet (ORCID: https://orcid.org/0000-0003-0785-0019)
- Olivier Dussurget (ORCID: https://orcid.org/0000-0001-9924-0837)
- Michael G. Connor (ORCID: https://orcid.org/0000-0002-5413-2338)
- Marie‐Anne Nahori (ORCID: https://orcid.org/0000-0002-4066-4528)
- Colin McGuckin (ORCID: https://orcid.org/0000-0001-5250-6810)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Sorbonne Université (FR)
- Institut National de la Transfusion Sanguine (FR)
- Service Régional Vaudois de Transfusion Sanguine (CH)
- Institut de Médecine Tropicale du Service de Santé des Armées (FR)
- Laboratoire de Physique des Plasmas (FR)
- Paris Biotech Santé (FR)
Publication Details
- Journal
- npj Regenerative Medicine
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1038/s41536-024-00372-0
- Citations
- 6
- Primary Topic
- Plasma Applications and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 2.43
Funders
- Agence Nationale de la Recherche
- Institut Pasteur
- Centre National de la Recherche Scientifique
- Université Sorbonne Paris Cité
- Leibniz-Gemeinschaft
- École Polytechnique, Université Paris-Saclay