IFN-λ is protective against lethal oralToxoplasma gondiiinfection

Abstract

AbstractInterferons are essential for innate and adaptive immune responses against a wide variety of pathogens. Interferon lambda (IFN-λ) protects mucosal barriers during pathogen exposure. The intestinal epithelium is the first contact site forToxoplasma gondii(T. gondii) with its hosts and the first defense line that limits parasite infection. Knowledge of very earlyT. gondiiinfection events in the gut tissue is limited and a possible contribution of IFN-λ has not been investigated so far. Here, we demonstrate with systemic interferon lambda receptor (IFNLR1) and conditional (Villin-Cre) knockout mouse models and bone marrow chimeras of oralT. gondiiinfection and mouse intestinal organoids a significant impact of IFN-λ signaling in intestinal epithelial cells and neutrophils toT. gondiicontrol in the gastrointestinal tract. Our results expand the repertoire of interferons that contribute to the control ofT. gondiiand may lead to novel therapeutic approaches against this world-wide zoonotic pathogen.