Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2
IntroductionLactic acid bacteria (LAB) are well known for their beneficial effects on the regulation of immune responses and host protection against microbial infections. We previously reported that heat-killed Enterococcus faecalis strain KH2 (heat-killed KH2), a species of LAB, enhances inflammato...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1550934/full |
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| author | Shiho Kurosaka Shiho Kurosaka Hiromasa Tanno Minako Hirose Wakana Kamada Rena Takayashiki Ikue Sone Yuki Sato Takumi Watanabe Shinyo Ishi Miki Shoji Yoshimichi Imai Ko Sato Keiko Ishii Hiromitsu Hara Sho Yamasaki Sho Yamasaki Sho Yamasaki Shinobu Saijo Yoichiro Iwakura Yoichiro Iwakura Kazuyoshi Kawakami Emi Kanno |
| author_facet | Shiho Kurosaka Shiho Kurosaka Hiromasa Tanno Minako Hirose Wakana Kamada Rena Takayashiki Ikue Sone Yuki Sato Takumi Watanabe Shinyo Ishi Miki Shoji Yoshimichi Imai Ko Sato Keiko Ishii Hiromitsu Hara Sho Yamasaki Sho Yamasaki Sho Yamasaki Shinobu Saijo Yoichiro Iwakura Yoichiro Iwakura Kazuyoshi Kawakami Emi Kanno |
| author_sort | Shiho Kurosaka |
| collection | DOAJ |
| description | IntroductionLactic acid bacteria (LAB) are well known for their beneficial effects on the regulation of immune responses and host protection against microbial infections. We previously reported that heat-killed Enterococcus faecalis strain KH2 (heat-killed KH2), a species of LAB, enhances inflammatory responses at wound sites and accelerates the skin wound healing process. In this study, we aimed to clarify the pathway underlying the wound-healing effects of heat-killed KH2. We focused on CARD9, a common adaptor molecule for C-type lectin receptors and Dectin-2, the upstream receptor for this adaptor molecule.MethodsFour full-thickness dermal wounds were created on the backs of wild-type (WT) mice, CARD9 KO mice, and Dectin-2 KO mice, and the effects of heat-killed KH2 administration were examined. We analyzed the percent wound closure, re-epithelialization, granulation tissue formation, and the production of inflammatory cytokines and chemokines.ResultsHeat-killed KH2 administration enhanced wound closure, granulation tissue formation, and re-epithelialization in WT mice. However, these effects were absent in heat-killed KH2-treated CARD9 KO mice. Similar results were observed in the migration of neutrophils and the production of TNF-α, IL-6, KC, and MIP-2 in heat-killed KH2-treated CARD9 KO mice. Furthermore, heat-killed KH-2 induced activation of reporter cells expressing Dectin-2. Finally, heat-killed KH-2 treatment in Dectin-2 KO mice did not promote skin wound healing.ConclusionThese results suggest that recognition of heat-killed KH2 by Dectin-2 may activate CARD9-mediated signaling, which may contribute to the promotion of skin wound healing through KH2 treatment. |
| format | Article |
| id | doaj-art-fd1580e91f2d418ea4c50cdba98a2691 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-fd1580e91f2d418ea4c50cdba98a26912025-08-20T02:32:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15509341550934Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2Shiho Kurosaka0Shiho Kurosaka1Hiromasa Tanno2Minako Hirose3Wakana Kamada4Rena Takayashiki5Ikue Sone6Yuki Sato7Takumi Watanabe8Shinyo Ishi9Miki Shoji10Yoshimichi Imai11Ko Sato12Keiko Ishii13Hiromitsu Hara14Sho Yamasaki15Sho Yamasaki16Sho Yamasaki17Shinobu Saijo18Yoichiro Iwakura19Yoichiro Iwakura20Kazuyoshi Kawakami21Emi Kanno22Department of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanBio-Lab Co., Ltd., Hidaka, JapanDepartment of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanBio-Lab Co., Ltd., Hidaka, JapanDepartment of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, JapanLaboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, JapanDivision of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanDivision of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, JapanDepartment of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan0Laboratory for Human Disease Models, Louis Pasteur Center for Medical Research, Kyoto, JapanDepartment of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Translational Science for Nursing, Tohoku University Graduate School of Medicine, Sendai, JapanIntroductionLactic acid bacteria (LAB) are well known for their beneficial effects on the regulation of immune responses and host protection against microbial infections. We previously reported that heat-killed Enterococcus faecalis strain KH2 (heat-killed KH2), a species of LAB, enhances inflammatory responses at wound sites and accelerates the skin wound healing process. In this study, we aimed to clarify the pathway underlying the wound-healing effects of heat-killed KH2. We focused on CARD9, a common adaptor molecule for C-type lectin receptors and Dectin-2, the upstream receptor for this adaptor molecule.MethodsFour full-thickness dermal wounds were created on the backs of wild-type (WT) mice, CARD9 KO mice, and Dectin-2 KO mice, and the effects of heat-killed KH2 administration were examined. We analyzed the percent wound closure, re-epithelialization, granulation tissue formation, and the production of inflammatory cytokines and chemokines.ResultsHeat-killed KH2 administration enhanced wound closure, granulation tissue formation, and re-epithelialization in WT mice. However, these effects were absent in heat-killed KH2-treated CARD9 KO mice. Similar results were observed in the migration of neutrophils and the production of TNF-α, IL-6, KC, and MIP-2 in heat-killed KH2-treated CARD9 KO mice. Furthermore, heat-killed KH-2 induced activation of reporter cells expressing Dectin-2. Finally, heat-killed KH-2 treatment in Dectin-2 KO mice did not promote skin wound healing.ConclusionThese results suggest that recognition of heat-killed KH2 by Dectin-2 may activate CARD9-mediated signaling, which may contribute to the promotion of skin wound healing through KH2 treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1550934/fullskin wound healingEnterococcus faecalis KH2C-type lectin receptorsCARD9Dectin-2 |
| spellingShingle | Shiho Kurosaka Shiho Kurosaka Hiromasa Tanno Minako Hirose Wakana Kamada Rena Takayashiki Ikue Sone Yuki Sato Takumi Watanabe Shinyo Ishi Miki Shoji Yoshimichi Imai Ko Sato Keiko Ishii Hiromitsu Hara Sho Yamasaki Sho Yamasaki Sho Yamasaki Shinobu Saijo Yoichiro Iwakura Yoichiro Iwakura Kazuyoshi Kawakami Emi Kanno Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2 Frontiers in Immunology skin wound healing Enterococcus faecalis KH2 C-type lectin receptors CARD9 Dectin-2 |
| title | Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2 |
| title_full | Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2 |
| title_fullStr | Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2 |
| title_full_unstemmed | Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2 |
| title_short | Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2 |
| title_sort | contribution of card9 signaling to wound healing in skin promoted by topical administration of heat killed enterococcus faecalis strain kh2 and the involvement of dectin 2 |
| topic | skin wound healing Enterococcus faecalis KH2 C-type lectin receptors CARD9 Dectin-2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1550934/full |
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