Inflammation induces two types of inflammatory dendritic cells in inflamed lymph nodes

ABSTRACT

The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64⁺CD11c⁺MHCII⁺ inflammatory DCs. Through the assessment of chemokine receptor dependency, gene expression profiles, growth factor requirements and DC-specific lineage mapping, we herein unveil a novel inflammatory DC population (we termed ‘CD64⁺ cDCs’) that arises from conventional DCs (cDCs), distinguishable from CD64⁺ monocyte-derived DCs (moDCs) in inflamed LNs. We determined that Listeria-induced type I IFN is a critical inflammatory cue for the development of CD64⁺ cDCs but not CD64⁺ moDCs. Importantly, CD64⁺ cDCs displayed a higher potential to activate T cells than CD64⁺ moDCs, whereas the latter showed more robust expression of inflammatory genes. Although CD64⁺ and CD64− cDCs were able to cross-present soluble antigens at a high dose to CD8⁺ T cells, CD64⁺ cDCs concentrated and cross-presented a minute amount of soluble antigens delivered via CD64 (FcγRI) as immune complexes. These findings reveal the role of early inflammatory responses in driving the differentiation of two inflammatory DC subsets empowered with distinct competencies.