Dr Tobias Steinfeldt (Freiburg i. Br. / DE), Mateo Murillo-Léon (Freiburg i. Br. / DE), Aura María Bastidas-Quintero (Freiburg i. Br. / DE), Niklas Sebastian Endres (Berlin / DE), Dr. Daniel Schnepf (London / GB), Dr. Estefanía Delgado Betancourt (Berlin / DE), Annette Ohnemus (Freiburg i. Br. / DE), Prof. Gregory Alan Taylor (Durham, NC / US), Prof. Martin Schwemmle (Freiburg i. Br. / DE), Prof. Peter Staeheli (Freiburg i. Br. / DE)
Abstract text
Toxoplasma gondii (T. gondii) is food-borne parasite that is an important cause of clinical disability in humans. Bradyzoites or sporozoites released upon rupture of tissue cysts or oocysts disseminate throughout the host. Interferons 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 for T. gondii with its hosts and the first defense line that limits parasite infection. Knowledge of very early T. gondii infection events in the gut tissue is limited and a possible contribution of IFN-λ has not been - to the best of our knowledge - investigated so far. Here, we demonstrate with systemic interferon lambda receptor (IFNLR1) and conditional (Villin-Cre) knockout (ko) mouse models of oral T. gondii infection and mouse intestinal organoids a significant impact of IFN-λ signalling in intestinal epithelial cells. Furthermore, a probe-based qPCR reveals increased parasite load in the ileum in ko compared with wt animals. Infective parasite stages cross the intestinal epithelial barrier to infect the lamina propria. In the lamina propria, T. gondii replicates in a variety of different cell types before disseminating throughout the host. Microsections of intestinal tissue demonstrate augmented T. gondii replication in the lamina propria of ko compared with wt animals. Besides intestinal epithelial cells, our results obtained with bone marrow-chimeras reveal an additional impact of IFN-λ signalling in neutrophils to parasite control. This study expands the repertoire of interferons that contribute to the control of T. gondii in mice and may lead to novel therapeutic approaches against this world-wide zoonotic pathogen.