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Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.
Tromp, Angelino T; Van Gent, Michiel; Abrial, Pauline; Martin, Amandine; Jansen, Joris P; De Haas, Carla J C; Van Kessel, Kok P M; Bardoel, Bart W; Kruse, Elisabeth; Bourdonnay, Emilie; Boettcher, Michael; McManus, Michael T; Day, Christopher J; Jennings, Michael P; Lina, Gérard; Vandenesch, François; Van Strijp, Jos A G; Lebbink, Robert Jan; Haas, Pieter-Jan A; Henry, Thomas; Spaan, András N.
Afiliación
  • Tromp AT; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Van Gent M; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Abrial P; Department of Microbiology, University of Chicago, Chicago, IL, USA.
  • Martin A; CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France.
  • Jansen JP; CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France.
  • De Haas CJC; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Van Kessel KPM; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Bardoel BW; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Kruse E; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Bourdonnay E; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Boettcher M; CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France.
  • McManus MT; Department of Microbiology and Immunology, UCSF Diabetes Center, Keck Center for Noncoding RNA, University of California, San Francisco, San Francisco, CA, USA.
  • Day CJ; Department of Microbiology and Immunology, UCSF Diabetes Center, Keck Center for Noncoding RNA, University of California, San Francisco, San Francisco, CA, USA.
  • Jennings MP; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
  • Lina G; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
  • Vandenesch F; CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France.
  • Van Strijp JAG; CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France.
  • Lebbink RJ; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Haas PA; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Henry T; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Spaan AN; CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, Hospices Civils de Lyon, Lyon, France. thomas.henry@inserm.fr.
Nat Microbiol ; 3(6): 708-717, 2018 06.
Article en En | MEDLINE | ID: mdl-29736038
The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus / Toxinas Bacterianas / Antígenos Comunes de Leucocito / Receptor de Anafilatoxina C5a / Exotoxinas / Leucocidinas Límite: Animals / Humans Idioma: En Revista: Nat Microbiol Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus / Toxinas Bacterianas / Antígenos Comunes de Leucocito / Receptor de Anafilatoxina C5a / Exotoxinas / Leucocidinas Límite: Animals / Humans Idioma: En Revista: Nat Microbiol Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido