Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin - Pass P3S - Publications - Protéomique
Journal Articles Science Year : 2022

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

András Spaan , Anna-Lena Neehus (1) , Emmanuel Laplantine (2) , Frederik Staels , Masato Ogishi , Yoann Seeleuthner (1) , Franck Rapaport , Keenan Lacey , Erika van Nieuwenhove , Maya Chrabieh (1) , David Hum , Mélanie Migaud (1) , Araksya Izmiryan (1) , Lazaro Lorenzo (1) , Tatiana Kochetkov , Dani Heesterbeek , Bart Bardoel , Ashley Dumont , Kerry Dobbs , Solenne Chardonnet (3, 4) , Søren Heissel , Timour Baslan , Peng Zhang , Rui Yang , Dusan Bogunovic , Herman Wunderink , Pieter-Jan Haas , Henrik Molina , Griet van Buggenhout , Stanislas Lyonnet (1) , Luigi Notarangelo , Mikko Seppänen , Robert Weil , Gisela Seminario , Héctor Gomez-Tello , Carine Wouters , Mehrnaz Mesdaghi , Mohammad Shahrooei , Xavier Bossuyt , Erdal Sag , Rezan Topaloglu , Seza Ozen , Helen Leavis , Maarten van Eijk , Liliana Bezrodnik , Lizbeth Blancas Galicia , Alain Hovnanian (1) , Aude Nassif , Brigitte Bader-Meunier (1) , Bénédicte Neven (1) , Isabelle Meyts , Rik Schrijvers , Anne Puel (1) , Jacinta Bustamante (1) , Ivona Aksentijevich , Daniel Kastner , Victor Torres , Stéphanie Humblet-Baron , Adrian Liston , Laurent Abel (1) , Bertrand Boisson (1) , Jean-Laurent Casanova (1)
András Spaan
Anna-Lena Neehus
Imagine - Institut des maladies génétiques (IHU)
Emmanuel Laplantine
Génomes, biologie cellulaire et thérapeutiques
Frederik Staels
Masato Ogishi
Yoann Seeleuthner
  • Function : Author
Imagine - Institut des maladies génétiques (IHU)
Franck Rapaport
Keenan Lacey
Erika van Nieuwenhove
Maya Chrabieh
  • Function : Author
Imagine - Institut des maladies génétiques (IHU)
David Hum
Mélanie Migaud
Imagine - Institut des maladies génétiques (IHU)
Araksya Izmiryan
Imagine - Institut des maladies génétiques (IHU)
Lazaro Lorenzo
Imagine - Institut des maladies génétiques (IHU)
Tatiana Kochetkov
  • Function : Author
Dani Heesterbeek
Bart Bardoel
Ashley Dumont
Kerry Dobbs
Solenne Chardonnet
Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé
Plateforme Post-génomique de la Pitié-Salpêtrière
CV
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
Imagine - Institut des maladies génétiques (IHU)
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
Imagine - Institut des maladies génétiques (IHU)
Aude Nassif
Brigitte Bader-Meunier
Imagine - Institut des maladies génétiques (IHU)
Bénédicte Neven
  • Function : Author
Imagine - Institut des maladies génétiques (IHU)
Isabelle Meyts
Rik Schrijvers
Anne Puel
Imagine - Institut des maladies génétiques (IHU)
Jacinta Bustamante
Imagine - Institut des maladies génétiques (IHU)
Ivona Aksentijevich
Daniel Kastner
Victor Torres
Stéphanie Humblet-Baron
Adrian Liston
Laurent Abel
Imagine - Institut des maladies génétiques (IHU)
Bertrand Boisson
Imagine - Institut des maladies génétiques (IHU)
Jean-Laurent Casanova
Imagine - Institut des maladies génétiques (IHU)

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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Life Sciences [q-bio]
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https://hal.sorbonne-universite.fr/hal-03810222

Submitted on : Tuesday, October 11, 2022-4:00:37 PM

Last modification on : Friday, April 19, 2024-3:20:03 PM

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

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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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