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

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Spaan , A N , Neehus , A-L , Laplantine , E , Staels , F , Ogishi , M , Seeleuthner , Y , Rapaport , F , Lacey , K A , Van Nieuwenhove , E , Chrabieh , M , Hum , D , Migaud , M , Izmiryan , A , Lorenzo , L , Kochetkov , T , Heesterbeek , D A C , Bardoel , B W , DuMont , A L , Dobbs , K , Chardonnet , S , Heissel , S , Baslan , T , Zhang , P , Yang , R , Bogunovic , D , Wunderink , H F , Haas , P-J A , Molina , H , Van Buggenhout , G , Lyonnet , S , Notarangelo , L D , Seppänen , M R J , Weil , R , Seminario , G , Gomez-Tello , H , Wouters , C , Mesdaghi , M , Shahrooei , M , Bossuyt , X , Sag , E , Topaloglu , R , Ozen , S , Leavis , H L , van Eijk , M M J , Bezrodnik , L , Galicia , L B , Hovnanian , A , Nassif , A , Bader-Meunier , B , Neven , B , Meyts , I , Schrijvers , R , Puel , A , Bustamante , J , Aksentijevich , I , Kastner , D L , Torres , V J , Humblet-Baron , S , Liston , A , Abel , L , Boisson , B & Casanova , J-L 2022 , ' Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin ' , Science , vol. 376 , no. 6599 , 6380 , pp. 1285-+ . https://doi.org/10.1126/science.abm6380

Title: Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin
Author: Spaan, Andras 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, Melanie; Izmiryan, Araksya; Lorenzo, Lazaro; Kochetkov, Tatiana; Heesterbeek, Dani A. C.; Bardoel, Bart W.; DuMont, Ashley L.; Dobbs, Kerry; Chardonnet, Solenne; Heissel, Soren; 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, Hector; Wouters, Carine; Mesdaghi, Mehrnaz; Shahrooei, Mohammad; Bossuyt, Xavier; Sag, Erdal; Topaloglu, Rezan; Ozen, Seza; Leavis, Helen L.; van Eijk, Maarten M. J.; Bezrodnik, Liliana; Galicia, Lizbeth Blancas; Hovnanian, Alain; Nassif, Aude; Bader-Meunier, Brigitte; Neven, Benedicte; Meyts, Isabelle; Schrijvers, Rik; Puel, Anne; Bustamante, Jacinta; Aksentijevich, Ivona; Kastner, Daniel L.; Torres, Victor J.; Humblet-Baron, Stephanie; Liston, Adrian; Abel, Laurent; Boisson, Bertrand; Casanova, Jean-Laurent
Contributor organization: Children's Hospital
HUS Children and Adolescents
Clinicum
Date: 2022-06-17
Language: eng
Number of pages: 63
Belongs to series: Science
ISSN: 0036-8075
DOI: https://doi.org/10.1126/science.abm6380
URI: http://hdl.handle.net/10138/346550
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 kappa B 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 alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.
Subject: PANTON-VALENTINE LEUKOCIDIN
PYOGENIC BACTERIAL-INFECTIONS
DU-CHAT-SYNDROME
HIDRADENITIS SUPPURATIVA
LINEAR UBIQUITIN
INBORN-ERRORS
AUREUS
CRI
HEMOLYSIN
PROTEIN
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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