Tolerance during infection

Abstract

Antigen-presenting cells (APCs) in the intestine maintain the delicate balance between the induction of immunity against invading pathogens and immune tolerance to food and commensal bacteria, but which APCs contribute to tolerance and how this changes during infection are unclear. In Science, Canesso et al. find that conventional type 1 dendritic cells (cDC1s) contribute to food-specific induction of peripheral regulatory T (pT_reg) cells, and infection impairs oral tolerance by reducing antigen presentation by cDC1 and RORγt⁺ APCs in the mesenteric lymph nodes (MLNs). cDC1, cDC2 and RORγt⁺ APCs presented dietary antigen to CD4⁺ T cells in the MLNs. cDC1s showed increased expression of genes associated with the generation of pT_reg cells, whereas cDC2s had higher expression of genes associated with T cell activation. Using a MHC-II knockout mouse model, food-specific differentiation of pT_reg cells was reduced in cDC1s but not cDC2s that lacked MHC-II expression. Following infection of mice with Strongyloides venezuelensis, food-specific induction of pT_reg cells was reduced, the presentation of dietary antigen by cDC1 or RORγt⁺ APCs in the MLNs was almost completely abrogated, and there was an increase in total numbers of cDC2s. Together, these data suggest that during infection, cDC1 and RORγt⁺ APCs are prevented from engaging in antigen presentation to dietary antigen-specific T cells owing to an increase in antigen presentation by cDC2s.

Original reference: Science https://doi.org/10.1126/science.ado5088 (2024)