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Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection.
Dong, Xintong; Limjunyawong, Nathachit; Sypek, Elizabeth I; Wang, Gaofeng; Ortines, Roger V; Youn, Christine; Alphonse, Martin P; Dikeman, Dustin; Wang, Yu; Lay, Mark; Kothari, Ruchita; Vasavda, Chirag; Pundir, Priyanka; Goff, Loyal; Miller, Lloyd S; Lu, Wuyuan; Garza, Luis A; Kim, Brian S; Archer, Nathan K; Dong, Xinzhong.
Afiliação
  • Dong X; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Limjunyawong N; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Sypek EI; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Wang G; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ortines RV; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Youn C; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Alphonse MP; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Dikeman D; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Wang Y; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lay M; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kothari R; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Vasavda C; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Pundir P; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Goff L; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Miller LS; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lu W; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Garza LA; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kim BS; Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Archer NK; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: narcher2@jhmi.edu.
  • Dong X; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD,
Immunity ; 55(9): 1645-1662.e7, 2022 09 13.
Article em En | MEDLINE | ID: mdl-35882236
ABSTRACT
Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a/b. Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion of Staphylococcus species. Defensins and Mrgpra2 were critical for combating S. aureus infections and the formation of neutrophil abscesses, a hallmark of antibacterial immunity. Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1ß and CXCL2 which are vital for proper amplification and propagation of the antibacterial immune response. This study demonstrated the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Bacterianas / Receptores Acoplados a Proteínas G / Neutrófilos Limite: Animals Idioma: En Revista: Immunity Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Bacterianas / Receptores Acoplados a Proteínas G / Neutrófilos Limite: Animals Idioma: En Revista: Immunity Ano de publicação: 2022 Tipo de documento: Article