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Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.
Spaan, András N; Neehus, Anna-Lena; Laplantine, Emmanuel; Staels, Frederik; Ogishi, Masato; Seeleuthner, Yoann; Rapaport, Franck; Lacey, Keenan A; Van Nieuwenhove, Erika; Chrabieh, Maya; Hum, David; Migaud, Mélanie; Izmiryan, Araksya; Lorenzo, Lazaro; Kochetkov, Tatiana; Heesterbeek, Dani A C; Bardoel, Bart W; DuMont, Ashley L; Dobbs, Kerry; Chardonnet, Solenne; Heissel, Søren; Baslan, Timour; Zhang, Peng; Yang, Rui; Bogunovic, Dusan; Wunderink, Herman F; Haas, Pieter-Jan A; Molina, Henrik; Van Buggenhout, Griet; Lyonnet, Stanislas; Notarangelo, Luigi D; Seppänen, Mikko R J; Weil, Robert; Seminario, Gisela; Gomez-Tello, Héctor; Wouters, Carine; Mesdaghi, Mehrnaz; Shahrooei, Mohammad; Bossuyt, Xavier; Sag, Erdal; Topaloglu, Rezan; Ozen, Seza; Leavis, Helen L; van Eijk, Maarten M J; Bezrodnik, Liliana; Blancas Galicia, Lizbeth; Hovnanian, Alain; Nassif, Aude; Bader-Meunier, Brigitte; Neven, Bénédicte.
Affiliation
  • Spaan AN; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
  • Neehus AL; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, Netherlands.
  • Laplantine E; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France.
  • Staels F; Imagine Institute, Paris Cité University, 75015 Paris, France.
  • Ogishi M; Institute of Experimental Hematology, REBIRTH Research Center for Translational and Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany.
  • Seeleuthner Y; Centre d'Immunologie et des Maladies Infectieuses, INSERM U1135, CNRS ERL8255, Sorbonne University, 75724 Paris, France.
  • Rapaport F; Institut de Recherche St. Louis, Hôpital St. Louis, INSERM U944, CNRS U7212, Paris Cité University, 75010 Paris, France.
  • Lacey KA; Laboratory for Adaptive Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium.
  • Van Nieuwenhove E; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
  • Chrabieh M; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France.
  • Hum D; Imagine Institute, Paris Cité University, 75015 Paris, France.
  • Migaud M; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
  • Izmiryan A; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Lorenzo L; Laboratory for Adaptive Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium.
  • Kochetkov T; Department of Pediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, Netherlands.
  • Heesterbeek DAC; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France.
  • Bardoel BW; Imagine Institute, Paris Cité University, 75015 Paris, France.
  • DuMont AL; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
  • Dobbs K; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France.
  • Chardonnet S; Imagine Institute, Paris Cité University, 75015 Paris, France.
  • Heissel S; Imagine Institute, Paris Cité University, 75015 Paris, France.
  • Baslan T; Laboratory of Genetic Skin Diseases, INSERM U1163, 75015 Paris, France.
  • Zhang P; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France.
  • Yang R; Imagine Institute, Paris Cité University, 75015 Paris, France.
  • Bogunovic D; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
  • Wunderink HF; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, Netherlands.
  • Haas PA; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, Netherlands.
  • Molina H; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • Van Buggenhout G; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD 20852, USA.
  • Lyonnet S; Plateforme Post-génomique de la Pitié-Salpêtrière, P3S, UMS Production et Analyse de données en Sciences de la vie et en Santé, PASS, INSERM, Sorbonne University, 75013 Paris, France.
  • Notarangelo LD; Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA.
  • Seppänen MRJ; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Weil R; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
  • Seminario G; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
  • Gomez-Tello H; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Wouters C; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, Netherlands.
  • Mesdaghi M; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, Netherlands.
  • Shahrooei M; Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA.
  • Bossuyt X; Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
  • Sag E; Center for Human Genetics, University Hospitals Leuven, 3000 Leuven, Belgium.
  • Topaloglu R; Imagine Institute, Paris Cité University, 75015 Paris, France.
  • Ozen S; Laboratory Embryology and Genetics of Malformations, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France.
  • Leavis HL; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD 20852, USA.
  • van Eijk MMJ; Rare Disease and Pediatric Research Centers, Children and Adolescents, University of Helsinki and HUS Helsinki University Hospital, 00260 Helsinki, Finland.
  • Bezrodnik L; Centre d'Immunologie et des Maladies Infectieuses, INSERM U1135, CNRS ERL8255, Sorbonne University, 75724 Paris, France.
  • Blancas Galicia L; Center for Clinical Immunology, Immunology Group Children's Hospital Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina.
  • Hovnanian A; Immunology Department, Poblano Children's Hospital, 72190 Puebla, Mexico.
  • Nassif A; Laboratory for Adaptive Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium.
  • Bader-Meunier B; Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium.
  • Neven B; Department of Allergy and Clinical Immunology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, 15468-155514 Tehran, Iran.
Science ; 376(6599): eabm6380, 2022 06 17.
Article in En | MEDLINE | ID: mdl-35587511
ABSTRACT
The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor κB signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor α-toxin. Naturally elicited antibodies against α-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to α-toxin in nonleukocytic cells.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endopeptidases / Staphylococcal Infections / Staphylococcus aureus / Bacterial Toxins / Cri-du-Chat Syndrome / Haploinsufficiency / Hemolysin Proteins Limits: Humans Language: En Journal: Science Year: 2022 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endopeptidases / Staphylococcal Infections / Staphylococcus aureus / Bacterial Toxins / Cri-du-Chat Syndrome / Haploinsufficiency / Hemolysin Proteins Limits: Humans Language: En Journal: Science Year: 2022 Document type: Article Affiliation country: Estados Unidos