Disruption of type III Interferon (IFN) genes Ifnl2 and Ifnl3 recapitulates loss of the type III IFN receptor in the mucosal antiviral response

Stefan T. Peterson, Washington University School of Medicine in St. Louis
Elizabeth A. Kennedy, Washington University School of Medicine in St. Louis
Pamela H. Brigleb, University of Pittsburgh School of Medicine
Gwen M. Taylor, University of Pittsburgh School of Medicine
Kelly Urbanek, University of Pittsburgh School of Medicine
Traci L. Bricker, Washington University School of Medicine in St. Louis
Sanghyun Lee, Washington University School of Medicine in St. Louis
Haina Shin, Washington University School of Medicine in St. Louis
Terence S. Dermody, University of Pittsburgh School of Medicine
Adrianus C.M. Boon, Washington University School of Medicine in St. Louis
Megan T. Baldridge, Washington University School of Medicine in St. Louis

Abstract

Type III interferon (IFN), or IFN lambda (IFN-λ), is an essential component of the innate immune response to mucosal viral infections. In both the intestine and the lung, signaling via the IFN-λ receptor (IFNLR) controls clinically important viral pathogens, including influenza virus, norovirus, and rotavirus. While it is thought that IFN-λ cytokines are the exclusive ligands for signaling through IFNLR, it is not known whether genetic ablation of these cytokines phenotypically recapitulates disruption of the receptor. Here, we report the serendipitous establishment of