| Literature DB >> 35587511 |
Anna-Lena Neehus1,2,3, Emmanuel Laplantine4,5, Frederik Staels6, Masato Ogishi7, Yoann Seeleuthner1,2, Franck Rapaport7, Stéphanie Humblet-Baron6, Adrian Liston6,8,9, Laurent Abel7,1,2, Bertrand Boisson7,1,2, Jean-Laurent Casanova7,1,2,10,11, András N Spaan7,12, Keenan A Lacey13, Erika Van Nieuwenhove6,14, Maya Chrabieh1,2, David Hum7, Mélanie Migaud1,2, Araksya Izmiryan2,15, Lazaro Lorenzo1,2, Tatiana Kochetkov7, Dani A C Heesterbeek12, Bart W Bardoel12, Ashley L DuMont13, Kerry Dobbs16, Solenne Chardonnet17, Søren Heissel18, Timour Baslan19, Peng Zhang7, Rui Yang7, Dusan Bogunovic20, Herman F Wunderink12, Pieter-Jan A Haas12, Henrik Molina18, Griet Van Buggenhout21,22, Stanislas Lyonnet2,23, Luigi D Notarangelo16, Mikko R J Seppänen24, Robert Weil4, Gisela Seminario25, Héctor Gomez-Tello26, Carine Wouters6,27, Mehrnaz Mesdaghi28, Mohammad Shahrooei29,30, Xavier Bossuyt29, Erdal Sag31, Rezan Topaloglu32, Seza Ozen31, Helen L Leavis33, Maarten M J van Eijk34, Liliana Bezrodnik25, Lizbeth Blancas Galicia35, Alain Hovnanian2,15,36, Aude Nassif37, Brigitte Bader-Meunier2,38,39, Bénédicte Neven2,38,39, Isabelle Meyts40,41, Rik Schrijvers42, Anne Puel7,1,2, Jacinta Bustamante7,1,2,43, Ivona Aksentijevich44, Daniel L Kastner44, Victor J Torres13.
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.Entities:
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Year: 2022 PMID： 35587511 PMCID： PMC9233084 DOI： 10.1126/science.abm6380
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714