Conventional dendritic cells (cDCs) are critical regulators of immunity, linking innate sensing to adaptive responses. Among them, type 2 cDCs (cDC2s) comprise two ontogenically distinct subsets, cDC2A and cDC2B, which exhibit non-redundant functions in peripheral tissues. However, how their production is regulated in the bone marrow during inflammation remains poorly understood.
Here, we asked whether haematopoiesis dynamically adapts cDC2 output to distinct infectious contexts. Using viral and helminth infection models, combined with lineage tracing and single-cell transcriptomics, we show that early inflammatory cues selectively shape the expansion and mobilisation of cDC2 precursors in an infection-specific manner. Influenza A virus infection preferentially expands and mobilises LysM⁺ pre-cDC2B cells via type I interferon–dependent signalling. In contrast, Nippostrongylus brasiliensis infection induces rapid egress of T-bet⁺ pre-cDC2A cells through IL-4–dependent mechanisms.
These results reveal that cDC2 subsets undergo divergent developmental programming during type 1 and type 2 immune responses, driven by cytokine signals acting directly at the precursor stage. We propose that the bone marrow functions as an early immune-sensing site that tailors dendritic cell output to the inflammatory context prior to antigen encounter. This immunity-matched regulation of cDC2 ontogeny represents a previously unappreciated layer of immune control with implications for the preconditioning of adaptive responses.