IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin
IntroductionAlthough 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 wo...
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| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984016/full |
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| author | Jean-Claude Lecron Jean-Claude Lecron Sandrine Charreau Sandrine Charreau Jean-François Jégou Nadjet Salhi Isabelle Petit-Paris Emmanuel Guignouard Christophe Burucoa Christophe Burucoa Laure Favot-Laforge Charles Bodet Anne Barra Anne Barra Vincent Huguier Vincent Huguier Jiad Mcheik Jiad Mcheik Laure Dumoutier Julien Garnier François-Xavier Bernard François-Xavier Bernard Bernhard Ryffel Franck Morel |
| author_facet | Jean-Claude Lecron Jean-Claude Lecron Sandrine Charreau Sandrine Charreau Jean-François Jégou Nadjet Salhi Isabelle Petit-Paris Emmanuel Guignouard Christophe Burucoa Christophe Burucoa Laure Favot-Laforge Charles Bodet Anne Barra Anne Barra Vincent Huguier Vincent Huguier Jiad Mcheik Jiad Mcheik Laure Dumoutier Julien Garnier François-Xavier Bernard François-Xavier Bernard Bernhard Ryffel Franck Morel |
| author_sort | Jean-Claude Lecron |
| collection | DOAJ |
| description | IntroductionAlthough 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.MethodsWe 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.ResultsAseptic 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.ConclusionThese 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. |
| first_indexed | 2024-04-12T09:36:19Z |
| format | Article |
| id | doaj.art-0d82be725e5f4162a27c8014f1a774a7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T09:36:19Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0d82be725e5f4162a27c8014f1a774a72022-12-22T03:38:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.984016984016IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skinJean-Claude Lecron0Jean-Claude Lecron1Sandrine Charreau2Sandrine Charreau3Jean-François Jégou4Nadjet Salhi5Isabelle Petit-Paris6Emmanuel Guignouard7Christophe Burucoa8Christophe Burucoa9Laure Favot-Laforge10Charles Bodet11Anne Barra12Anne Barra13Vincent Huguier14Vincent Huguier15Jiad Mcheik16Jiad Mcheik17Laure Dumoutier18Julien Garnier19François-Xavier Bernard20François-Xavier Bernard21Bernhard Ryffel22Franck Morel23Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Immunologie et Inflammation, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceQima-Bioalternatives (Qima Life Sciences), Gençay, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire de Bactériologie, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceLaboratoire Immunologie et Inflammation, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceService de Chirurgie Plastique, Centre Hospitalier et Universitaire (CHU) de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceService de Chirurgie Pédiatrique, Centre Hospitalier et Universitaire CHU) de Poitiers, Poitiers, FranceDe Duve Institute, Université catholique de Louvain, Brussels, BelgiumQima-Bioalternatives (Qima Life Sciences), Gençay, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceQima-Bioalternatives (Qima Life Sciences), Gençay, FranceLaboratoire 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, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, UR15560, Université de Poitiers, Poitiers, FranceIntroductionAlthough 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.MethodsWe 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.ResultsAseptic 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.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.984016/fullskinwound healingcytokineTh17pathogeninflammation |
| spellingShingle | Jean-Claude Lecron Jean-Claude Lecron Sandrine Charreau Sandrine Charreau Jean-François Jégou Nadjet Salhi Isabelle Petit-Paris Emmanuel Guignouard Christophe Burucoa Christophe Burucoa Laure Favot-Laforge Charles Bodet Anne Barra Anne Barra Vincent Huguier Vincent Huguier Jiad Mcheik Jiad Mcheik Laure Dumoutier Julien Garnier François-Xavier Bernard François-Xavier Bernard Bernhard Ryffel Franck Morel IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin Frontiers in Immunology skin wound healing cytokine Th17 pathogen inflammation |
| title | IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin |
| title_full | IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin |
| title_fullStr | IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin |
| title_full_unstemmed | IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin |
| title_short | IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin |
| title_sort | il 17 and il 22 are pivotal cytokines to delay wound healing of s aureus and p aeruginosa infected skin |
| topic | skin wound healing cytokine Th17 pathogen inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984016/full |
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