Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity.

Autor: Strine MS; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA., Alfajaro MM; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA., Graziano VR; Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA., Song J; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA., Hsieh LL; Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Hill R; Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Guo J; Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA., VanDussen KL; Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA., Orchard RC; Department of Immunology, University of Texas Southwestern Medical School, Dallas, TX, USA., Baldridge MT; Department of Medicine, Division of Infectious Diseases, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, Saint Louis, MO, USA., Lee S; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA. Electronic address: sanghyun_lee@brown.edu., Wilen CB; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: craig.wilen@yale.edu.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2022 Nov 08; Vol. 41 (6), pp. 111593.
DOI: 10.1016/j.celrep.2022.111593
Abstrakt: Murine norovirus (MNoV) is a model for human norovirus and for interrogating mechanisms of viral tropism and persistence. We previously demonstrated that the persistent strain MNoV CR6 infects tuft cells, which are dispensable for the non-persistent strain MNoV CW3 . We now show that diverse MNoV strains require tuft cells for chronic enteric infection. We also demonstrate that interferon-λ (IFN-λ) acts directly on tuft cells to cure chronic MNoV CR6 infection and that type I and III IFNs signal together via STAT1 in tuft cells to restrict MNoV CW3 tropism. We then develop an enteroid model and find that MNoV CR6 and MNoV CW3 similarly infect tuft cells with equal IFN susceptibility, suggesting that IFN derived from non-epithelial cells signals on tuft cells in trans to restrict MNoV CW3 tropism. Thus, tuft cell tropism enables MNoV persistence and is determined by tuft cell-intrinsic factors (viral receptor expression) and -extrinsic factors (immunomodulatory signaling by non-epithelial cells).
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE