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Ablation of Adar1 in myeloid cells imprints a global antiviral state in the lung and heightens early immunity against SARS-CoV-2.
Adamska, Julia Z; Verma, Rohit; Gupta, Shakti; Hagan, Thomas; Wimmers, Florian; Floyd, Katharine; Li, Qin; Valore, Erika V; Wang, Yanli; Trisal, Meera; Vilches-Moure, José G; Subramaniam, Shankar; Walkley, Carl R; Suthar, Mehul S; Li, Jin Billy; Pulendran, Bali.
  • Adamska JZ; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94304, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Verma R; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94304, USA.
  • Gupta S; Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
  • Hagan T; Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
  • Wimmers F; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94304, USA.
  • Floyd K; Department of Pediatrics, Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Center, Emory School of Medicine, Atlanta, GA 30329, USA.
  • Li Q; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Valore EV; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94304, USA.
  • Wang Y; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94304, USA.
  • Trisal M; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94304, USA.
  • Vilches-Moure JG; Department of Comparative Medicine, Stanford University, Stanford, CA 94305, USA.
  • Subramaniam S; Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
  • Walkley CR; St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia.
  • Suthar MS; Department of Pediatrics, Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Center, Emory School of Medicine, Atlanta, GA 30329, USA.
  • Li JB; Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
  • Pulendran B; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94304, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Microbiology & Immunology, Stanford University, Stanford, CA 94305, US
Cell Rep ; 42(1): 112038, 2023 01 31.
Article in English | MEDLINE | ID: covidwho-2177166
ABSTRACT
Under normal homeostatic conditions, self-double-stranded RNA (self-dsRNA) is modified by adenosine deaminase acting on RNA 1 (ADAR1) to prevent the induction of a type I interferon-mediated inflammatory cascade. Antigen-presenting cells (APCs) sense pathogen-associated molecular patterns, such as dsRNA, to activate the immune response. The impact of ADAR1 on the function of APCs and the consequences to immunity are poorly understood. Here, we show that ADAR1 deletion in CD11c+ APCs leads to (1) a skewed myeloid cell compartment enriched in inflammatory cDC2-like cells, (2) enhanced numbers of activated tissue resident memory T cells in the lung, and (3) the imprinting of a broad antiviral transcriptional signature across both immune and non-immune cells. The resulting changes can be partially reversed by blocking IFNAR1 signaling and promote early resistance against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our study provides insight into the consequences of self-dsRNA sensing in APCs on the immune system.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Cell Rep Year: 2023 Document Type: Article Affiliation country: J.celrep.2023.112038

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Cell Rep Year: 2023 Document Type: Article Affiliation country: J.celrep.2023.112038