STAG Priming Preserves Paneth Cells and Limits Parasite-Triggered Ileitis

Toxoplasma gondii triggered ileitis is a commonly used model for diseases affecting the small intestine, such as Crohn's Disease. Inflammation is primarily dependent on Th1-mediated killing of Paneth cells, which consequently promotes intestinal dysbiosis and boosts inflammation and pathology in the organs. Priming of the immune system with soluble Toxoplasma antigen (STAG) has been shown to induce immune regulation in several inflammatory diseases. Herein, we describe how protection of Paneth cells by priming with STAG is associated with protection against T. gondii triggered ileitis. We observed that STAG priming diminished intestinal pathology and modulated cytokine profile, and specifically downregulates interferon expression. Consequently, priming with STAG sustained Paneth-cell numbers during infection, unlike non-immunized controls, and thus also retained antimicrobial protein expression. Interestingly, we show that naturally resistant BALB/c mice did not undergo total Paneth-cell ablation, but upon additional Paneth-cell depletion, presented intestinal pathology and tissue parasitism levels similar to susceptible C57BL/6. Finally, we show that the STAG-primed groups presented a different intestinal microbiota, primarily through promotion of a protective microbiota enriched in Firmicutes and depleted of Enterobacteriaceae. Thus, the results suggest that priming with STAG is able to prevent Paneth-cell depletion and is associated with resistance to T. gondii triggered ileitis.