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Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins.
Zhou, Quan D; Chi, Xun; Lee, Min Sub; Hsieh, Wei Yuan; Mkrtchyan, Jonathan J; Feng, An-Chieh; He, Cuiwen; York, Autumn G; Bui, Viet L; Kronenberger, Eliza B; Ferrari, Alessandra; Xiao, Xu; Daly, Allison E; Tarling, Elizabeth J; Damoiseaux, Robert; Scumpia, Philip O; Smale, Stephen T; Williams, Kevin J; Tontonoz, Peter; Bensinger, Steven J.
Afiliación
  • Zhou QD; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Chi X; Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China.
  • Lee MS; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Hsieh WY; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Mkrtchyan JJ; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Feng AC; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • He C; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • York AG; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Bui VL; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Kronenberger EB; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
  • Ferrari A; Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
  • Xiao X; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Daly AE; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Tarling EJ; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Damoiseaux R; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Scumpia PO; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Smale ST; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Williams KJ; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Tontonoz P; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Bensinger SJ; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Nat Immunol ; 21(7): 746-755, 2020 07.
Article en En | MEDLINE | ID: mdl-32514064
ABSTRACT
Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fagocitos / Estreptolisinas / Infecciones Bacterianas / Toxinas Bacterianas / Interferones / Hidroxicolesteroles Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fagocitos / Estreptolisinas / Infecciones Bacterianas / Toxinas Bacterianas / Interferones / Hidroxicolesteroles Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos