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

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Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal a-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; Galicia, Lizbeth Blancas; Hovnanian, Alain; Nassif, Aude; Bader-Meunier, Brigitte; Neven, Bénédicte; Meyts, Isabelle; Schrijvers, Rik; Puel, Anne; Bustamante, Jacinta; Aksentijevich, Ivona; Kastner, Daniel L.; Torres, Victor J.; Humblet-Baron, Stéphanie; Liston, Adrian; Abel, Laurent; Boisson, Bertrand; Casanova, Jean Laurent
(2022) Science, volume 376, issue 6599
(Article)
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 ... read more
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Keywords: Bacterial Toxins/immunology, Cri-du-Chat Syndrome/genetics, Endopeptidases/genetics, Haploinsufficiency/genetics, Hemolysin Proteins/immunology, Host-Pathogen Interactions/genetics, Humans, Immunity, Cellular/genetics, Necrosis, Staphylococcal Infections/genetics, Staphylococcus aureus, General, Journal Article
DOI: https://doi.org/10.1126/science.abm6380
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science
Note: Funding Information: This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) (UL1TR001866 to The Rockefeller University), the Sackler Center for Biomedicine and Nutrition at the Center for Clinical and Translational Science at The Rockefeller University and the Shapiro-Silverberg Fund for the Advancement of Translational Research (to A.N.S.), NIH P01AI061093 (to J.-L.C.), the Square Foundation, the French National Research Agency (ANR-10-IAHU-01, ANR-21-CE17-0014-03, ANR 14-CE15-0009-01, and ANR-15-CE17-0014), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the Howard Hughes Medical Institute, the St. Giles Foundation, The Rockefeller University, Institut National de la Santé et de la Recherche Médicale (INSERM), the Paris Cité University, the Laura and Isaac Perlmutter Cancer Center and the National Institutes of Health/National Cancer Institute (P30CA016087 to NYU Langone’s Rodent Genetic Engineering Laboratory), the Bettencourt Schueller Foundation and the International PhD program of the Imagine Institute (to A.-L.N.), the David Rockefeller Graduate Program (to M.O.), the New York Hideyo Noguchi Memorial Society (to M.O.), the Funai Foundation for Information Technology (to M.O.), the Honjo International Scholarship Foundation (to M.O.), the Cystic Fibrosis Foundation Postdoctoral Research Fellowship award (LACEY19FO to K.A.L.), the William C. and Joyce C. O’Neil Charitable Trust (to T.B.), the Memorial Sloan Kettering Single Cell Sequencing Initiative (to T.B.), the Hospital Research Funds at the Pediatric Research Center at the Helsinki University Hospital (to M.R.J.S.), and the Foundation for Pediatric Research of Finland (to M.R.J.S.). C.W. serves as a member of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (739543). The work was supported in part by the ERC Start grant IMMUNO (ERC-2010-StG_20091118 to A.L.), the VIB Grand Challenges (to A.L., S.H.-B., and R.S.), the KU Leuven BOFZAP start-up grant (to S.H.-B.), National Fund for Scientific Research senior clinical investigator fellowships (1805518N to R.S. and G0B5120N to I.M.), National Fund for Scientific Research grants (G0E8420N and G0C8517N to I.M.), a KU Leuven C1 grant (to I.M.), and the ERC Start grant MORE2ADA2 (ERC-2020-StG_948959 to I.M.). I.M. is a member of ERN-RITA. D.B. is supported by the NIH (R01 AI148963) and a founder of Lab11 Therapeutics Inc. The S. aureus work in the Torres laboratory is funded by the NIH (R01 AI099394, R01 AI105129, R01 AI121244, R01 AI137336, and R01 AI140754 to V.J.T.). V.J.T. is a Burroughs Wellcome Fund Investigator in the pathogenesis of infectious diseases. A.N.S. was supported in part by the European Union’s Horizon 2020 Research and Innovation Program (Marie Skłodowska-Curie grant 789645), the Dutch Research Council Talent Program (NWO Rubicon grant 019.171LW.015, partially nonstipendiary), and the European Molecular Biology Organization (EMBO Long-Term Fellowship grant ALTF 84-2017, nonstipendiary). Publisher Copyright: Copyright © 2022 The Authors, some rights reserved.
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