Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin - Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé - UMS 37 PASS Access content directly
Journal Articles Science Year : 2022

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin

András Spaan
Anna-Lena Neehus
Emmanuel Laplantine
Frederik Staels
Masato Ogishi
Yoann Seeleuthner
  • Function : Author
Franck Rapaport
Keenan Lacey
Erika van Nieuwenhove
Maya Chrabieh
  • Function : Author
David Hum
Mélanie Migaud
Araksya Izmiryan
Lazaro Lorenzo
Tatiana Kochetkov
  • Function : Author
Dani Heesterbeek
Bart Bardoel
Ashley Dumont
Kerry Dobbs
Søren Heissel
  • Function : Author
Timour Baslan
  • Function : Author
Peng Zhang
Rui Yang
Dusan Bogunovic
  • Function : Author
Herman Wunderink
Pieter-Jan Haas
  • Function : Author
Henrik Molina
Griet van Buggenhout
  • Function : Author
Stanislas Lyonnet
  • Function : Author
Luigi Notarangelo
Mikko Seppänen
Robert Weil
Gisela Seminario
  • Function : Author
Héctor Gomez-Tello
Carine Wouters
Mehrnaz Mesdaghi
Mohammad Shahrooei
  • Function : Author
Xavier Bossuyt
  • Function : Author
Erdal Sag
Rezan Topaloglu
Seza Ozen
Helen Leavis
Maarten van Eijk
Liliana Bezrodnik
  • Function : Author
Lizbeth Blancas Galicia
Alain Hovnanian
Aude Nassif
Brigitte Bader-Meunier
Bénédicte Neven
  • Function : Author
Isabelle Meyts
Rik Schrijvers
Anne Puel
Jacinta Bustamante
Ivona Aksentijevich
Daniel Kastner
Victor Torres
Stéphanie Humblet-Baron
Adrian Liston
Laurent Abel
Bertrand Boisson
Jean-Laurent Casanova


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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Dates and versions

hal-03810222 , version 1 (11-10-2022)



András Spaan, Anna-Lena Neehus, Emmanuel Laplantine, Frederik Staels, Masato Ogishi, et al.. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin. Science, 2022, 376 (6599), ⟨10.1126/science.abm6380⟩. ⟨hal-03810222⟩
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