Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation

The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b(+) conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b(+) cDCs belong to a unique SIRP alpha(+) cDC subset. At steady state, cDCs and TIM-4(+) macrophages are mainly located in T-cell zones, i.e., interfollicular regions, whereas a majority of subepithelial phagocytes are monocyte-derived cells, namely, LysoDCs and TIM-4(+) macrophages. Finally, oral administration of a Toll-like receptor 7 ligand induces at least three TNF-dependent events: (i) migration of dome-associated villus cDCs in interfollicular regions, (ii) increase of CD8 alpha(+) interfollicular cDC number, and (iii) activation of both CD11 alpha(+) and CD8 alpha(+) interfollicular cDCs. The latter is marked by a genetic reprograming leading to the upregulation of type I interferon-stimulated and of both immuno-stimulatory and -inhibitory gene expression.