GSE182984
Gene expression of murine DCs from bone marrow and spleen
Next to driving hematopoiesis, the bone marrow (BM) also serves as a secondary lymphoid organ, as it can drive T cell priming by resident dendritic cells (DC). When analyzing these DCs in murine BM, we uncovered that they are localized around sinusoids, can (cross)-present antigens, become activated upon intravenous LPS-injection, and for the majority belong to the cDC2 subtype which is associated with Th2/Th17 immunity. Gene-expression profiling revealed that BM-resident DCs are enriched for several c-type lectins, including Dectin-1, which can bind beta-glucans expressed on fungi and yeast. Indeed, DCs in BM were much more efficient in phagocytosis of both yeast-derived zymosan-particles and Aspergillus than their splenic counterparts, which was highly dependent on Dectin-1. DCs in human BM could also phagocytose zymosan, which was dependent on ß1-integrins. Moreover, zymosan-stimulated BM-resident DCs enhanced the differentiation of hematopoietic stem and progenitor cells towards neutrophils, while also boosting the maintenance of these progenitors. Our findings signify an important role for BM DCs as translators between infection and hematopoiesis, in particular in anti-fungal immunity. The ability of BM-resident DCs to boost granulopoiesis is relevant from a clinical perspective, and contributes to our understanding of the increased susceptibility for fungal infections following BM damage. Overall design: mRNA profiles of sort-purified dendritic cells from spleen or bone marrow from wildtype, healthy, adult mice.