@article{29c36af116ae411b8c89cd07816b4bd0,
title = "Homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium",
abstract = "Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial micro-biota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor (Ifnlr1), and is associated with IFN-λ production by leukocytes. Strikingly, imaging of these homeostatic ISGs reveals localization to pockets of the epithelium and concentration in mature IECs. Correspondingly, a minority of mature IECs express these ISGs in public single-cell RNA sequencing datasets from mice and humans. Furthermore, we assessed the ability of orally administered bacterial components to restore localized ISGs in mice lacking bacterial microbiota. Lastly, we find that IECs lacking Ifnlr1 are hyper-susceptible to initiation of murine rotavirus infection. These observations indicate that bacterial microbiota stimulate ISGs in localized regions of the intestinal epithelium at homeostasis, thereby preemptively activating antiviral defenses in vulnerable IECs to improve host defense against enteric viruses.",
author = "{Van Winkle}, {Jacob A.} and Peterson, {Stefan T.} and Kennedy, {Elizabeth A.} and Wheadon, {Michael J.} and Harshad Ingle and Chandni Desai and Rachel Rodgers and Constant, {David A.} and Wright, {Austin P.} and Lena Li and Artyomov, {Maxim N.} and Sanghyun Lee and Baldridge, {Megan T.} and Nice, {Timothy J.}",
note = "Funding Information: The authors would like to thank the following OHSU core facilities: Integrated Genomics Laboratory, Advanced Light Microscopy Core, and Histopathology Core; and the following WUSTL core facilities: Genome Technology Access Center. TJN was supported by NIH grant R01-AI130055 and by a faculty development award from the Sunlin & Priscilla Chou Foundation. JAV was supported by NIH grants T32-GM071338 and T32-AI007472. MTB was supported by NIH grants R01-AI139314, R01-AI141716, and R01-AI141478, the Pew Biomedical Scholars Program of the Pew Charitable Trusts, and a Children{\textquoteright}s Discovery Institute of Washington University and St Louis Children{\textquoteright}s Hospital Interdisciplinary Research Initiative grant (MI-II-2019–790). The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} Van Winkle et al.",
year = "2022",
month = feb,
doi = "10.7554/ELIFE.74072",
language = "English",
volume = "11",
journal = "eLife",
issn = "2050-084X",
}