IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin.

Autor:	Lecron JC; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.; Laboratoire Immunologie et Inflammation, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, France., Charreau S; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.; Qima-Bioalternatives (Qima Life Sciences), Gençay, France., Jégou JF; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France., Salhi N; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France., Petit-Paris I; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France., Guignouard E; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France., Burucoa C; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.; Laboratoire de Bactériologie, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, France., Favot-Laforge L; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France., Bodet C; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France., Barra A; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.; Laboratoire Immunologie et Inflammation, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, France., Huguier V; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.; Service de Chirurgie Plastique, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, France., Mcheik J; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.; Service de Chirurgie Pédiatrique, Centre Hospitalier et Universitaire CHU) de Poitiers, Poitiers, France., Dumoutier L; De Duve Institute, Université catholique de Louvain, Brussels, Belgium., Garnier J; Qima-Bioalternatives (Qima Life Sciences), Gençay, France., Bernard FX; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.; Qima-Bioalternatives (Qima Life Sciences), Gençay, France., Ryffel B; Laboratoire d'Immunologie et Neurogénétique Expérimentales et Moléculaire (INEM) - Unité Mixte de Recherche (UMR) 7355, Centre National de la Recherche Scientifique (CNRS) et Université d'Orléans, Orléans, France., Morel F; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Oct 07; Vol. 13, pp. 984016. Date of Electronic Publication: 2022 Oct 07 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.984016
Abstrakt:	Introduction: Although the presence of pathogens in skin wounds is known to delay the wound healing process, the mechanisms underlying this delay remain poorly understood. In the present study, we have investigated the regulatory role of proinflammatory cytokines on the healing kinetics of infected wounds. Methods: We have developed a mouse model of cutaneous wound healing, with or without wound inoculation with Staphylococcus aureus and Pseudomonas aeruginosa , two major pathogens involved in cutaneous wound bacterial infections. Results: Aseptic excision in C57BL/6 mouse skin induced early expression of IL-1β, TNFα and Oncostatin M (OSM), without detectable expression of IL-22 and IL-17A/F. S. aureus and P. aeruginosa wound inoculation not only increased the expression of IL-1β and OSM, but also induced a strong cutaneous expression of IL-22, IL-17A and IL-17F, along with an increased number of infiltrating IL-17A and/or IL-22-producing γδ T cells. The same cytokine expression pattern was observed in infected human skin wounds. When compared to uninfected wounds, mouse skin infection delayed the wound healing process. Injection of IL-1α, TNFα, OSM, IL-22 and IL-17 together in the wound edges induced delayed wound healing similar to that induced by the bacterial infection. Wound healing experiments in infected Rag2KO mice (deficient in lymphocytes) showed a wound healing kinetic similar to uninfected Rag2KO mice or WT mice. Rag2KO infected-skin lesions expressed lower levels of IL-17 and IL-22 than WT, suggesting that the expression of these cytokines is mainly dependent on γδ T cells in this model. Wound healing was not delayed in infected IL-17R/IL-22KO, comparable to uninfected control mice. Injection of recombinant IL-22 and IL-17 in infected wound edges of Rag2KO mice re-establish the delayed kinetic of wound healing, as in infected WT mice. Conclusion: These results demonstrate the synergistic and specific effects of IL-22 and IL-17 induced by bacterial infection delay the wound healing process, regardless of the presence of bacteria per se . Therefore, these cytokines play an unexpected role in delayed skin wound healing. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Lecron, Charreau, Jégou, Salhi, Petit-Paris, Guignouard, Burucoa, Favot-Laforge, Bodet, Barra, Huguier, Mcheik, Dumoutier, Garnier, Bernard, Ryffel and Morel.)
Databáze:	MEDLINE
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