Unlocking the Secrets of T. Arnold: a commensal protist that restrains virus-mediated loss of oral tolerance to gluten 2649

Abstract Description The mucosal immune system fosters a delicate regulatory environment that maintains oral food tolerance. Tolerance to food antigens results via the induction of peripheral regulatory T cells (pTreg) and their regulatory suppressive functions. Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specific T helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. Whether certain commensals can moderate virus-mediated LOT remains elusive. Using a Gluten-specific tetramer mouse model, we discovered that the gut-colonizing protist Tritrichomonas (T.) arnold protects against reovirus- and murine norovirus-mediated LOT. Mechanistically, T. arnold directly restrained the proinflammatory program in dietary antigen-presenting DCs. Furthermore, we uncovered that reovirus infection can prolong the breakage of oral tolerance to gluten by promoting gluten-specific Th1 and limiting Treg cell responses. Our current work focuses on identifying if T.arnold can restore oral tolerance once it is broken via a reovirus infection. Finally, analysis of fecal microbiomes showed that T. arnold-related Parabasalid strains are underrepresented in human CeD patients. Altogether, these findings will motivate further exploration of oral-tolerance-promoting protists in CeD and other immune-mediated food sensitivities. Funding Sources This work is supported by Luzmariel’s NIDDK F31 (DK138621) and T32 (AI089443) funding sources. Topic Categories Basic Autoimmunity (BA)