Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda

Summary: Cell-intrinsic antiviral gene expression by intestinal epithelial cells (IECs) limits infection by enteric viral pathogens. Here, we find that neonatal IECs express antiviral genes at homeostasis that depend on interferon lambda (IFN-λ) and are required for early control of mouse rotavirus...

Full description

Saved in:
Bibliographic Details
Main Authors: Bryan Ramirez Reyes, Shelby Madden, Kimberly A. Meyer, Brenden Bartsch, Austin P. Wright, David A. Constant, Timothy J. Nice
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725000142
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832557577710338048
author Bryan Ramirez Reyes
Shelby Madden
Kimberly A. Meyer
Brenden Bartsch
Austin P. Wright
David A. Constant
Timothy J. Nice
author_facet Bryan Ramirez Reyes
Shelby Madden
Kimberly A. Meyer
Brenden Bartsch
Austin P. Wright
David A. Constant
Timothy J. Nice
author_sort Bryan Ramirez Reyes
collection DOAJ
description Summary: Cell-intrinsic antiviral gene expression by intestinal epithelial cells (IECs) limits infection by enteric viral pathogens. Here, we find that neonatal IECs express antiviral genes at homeostasis that depend on interferon lambda (IFN-λ) and are required for early control of mouse rotavirus (mRV) infection. Neonatal homeostatic IFN-λ responses are independent of microbiota and pervasively distributed among IECs, distinguishing them from the homeostatic responses of adult mice. Developmental differences in homeostatic IFN-stimulated gene signatures of the intestine are regulated by maturation during the suckling-to-weanling transition, which includes reduced expression of Prdm1 by mature IECs. These studies identify developmental regulation of the homeostatic IFN-λ response, which is present in the neonatal intestine from birth, stimulated independent of microbiota, and preemptively protects IECs from viral infection. This intrinsically programmed antiviral response in early life is particularly important due to the absence of a robust microbiota or protective immune memory at birth, when the risk of enteric infection is high.
format Article
id doaj-art-5f5971f2980c4cf99d5bda84e66092fc
institution Kabale University
issn 2211-1247
language English
publishDate 2025-02-01
publisher Elsevier
record_format Article
series Cell Reports
spelling doaj-art-5f5971f2980c4cf99d5bda84e66092fc2025-02-03T04:16:40ZengElsevierCell Reports2211-12472025-02-01442115243Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambdaBryan Ramirez Reyes0Shelby Madden1Kimberly A. Meyer2Brenden Bartsch3Austin P. Wright4David A. Constant5Timothy J. Nice6Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USADepartment of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USADepartment of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USADepartment of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USADepartment of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USADepartment of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USADepartment of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA; Corresponding authorSummary: Cell-intrinsic antiviral gene expression by intestinal epithelial cells (IECs) limits infection by enteric viral pathogens. Here, we find that neonatal IECs express antiviral genes at homeostasis that depend on interferon lambda (IFN-λ) and are required for early control of mouse rotavirus (mRV) infection. Neonatal homeostatic IFN-λ responses are independent of microbiota and pervasively distributed among IECs, distinguishing them from the homeostatic responses of adult mice. Developmental differences in homeostatic IFN-stimulated gene signatures of the intestine are regulated by maturation during the suckling-to-weanling transition, which includes reduced expression of Prdm1 by mature IECs. These studies identify developmental regulation of the homeostatic IFN-λ response, which is present in the neonatal intestine from birth, stimulated independent of microbiota, and preemptively protects IECs from viral infection. This intrinsically programmed antiviral response in early life is particularly important due to the absence of a robust microbiota or protective immune memory at birth, when the risk of enteric infection is high.http://www.sciencedirect.com/science/article/pii/S2211124725000142CP: Immunology
spellingShingle Bryan Ramirez Reyes
Shelby Madden
Kimberly A. Meyer
Brenden Bartsch
Austin P. Wright
David A. Constant
Timothy J. Nice
Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda
Cell Reports
CP: Immunology
title Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda
title_full Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda
title_fullStr Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda
title_full_unstemmed Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda
title_short Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda
title_sort homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda
topic CP: Immunology
url http://www.sciencedirect.com/science/article/pii/S2211124725000142
work_keys_str_mv AT bryanramirezreyes homeostaticantiviralprotectionoftheneonatalgutepitheliumbyinterferonlambda
AT shelbymadden homeostaticantiviralprotectionoftheneonatalgutepitheliumbyinterferonlambda
AT kimberlyameyer homeostaticantiviralprotectionoftheneonatalgutepitheliumbyinterferonlambda
AT brendenbartsch homeostaticantiviralprotectionoftheneonatalgutepitheliumbyinterferonlambda
AT austinpwright homeostaticantiviralprotectionoftheneonatalgutepitheliumbyinterferonlambda
AT davidaconstant homeostaticantiviralprotectionoftheneonatalgutepitheliumbyinterferonlambda
AT timothyjnice homeostaticantiviralprotectionoftheneonatalgutepitheliumbyinterferonlambda