Transcriptional profiling reveals monocyte-related macrophages phenotypically resembling DC in human intestine

The tissue dendritic cell (DC) compartment is heterogeneous, and the ontogeny and functional specialization of human tissue conventional DC (cDC) subsets and their relationship with monocytes is unresolved. Here we identify monocyte-related CSF1R(+)Flt3(-) antigen presenting cells (APCs) that constitute about half of the cells classically defined as SIRP alpha(+) DCs in the steady-state human small intestine. CSF1R(+)Flt3(-) APCs express calprotectin and very low levels of CD14, are transcriptionally related to monocyte-derived cells, and accumulate during inflammation. CSF1R(+)Flt3(-) APCs show typical macrophage characteristics functionally distinct from their FltD3(+) cDC counterparts: under steady-state conditions they excel at antigen uptake, have a lower migratory potential, and are inefficient activators of naive T cells. These results have important implications for the understanding of the ontogenetic and functional heterogeneity within human tissue DCs and their relation to the monocyte lineage.