Abstract
Apart from controlling hematopoiesis, the bone marrow (BM) also serves as a secondary lymphoid organ, as it can induce naïve T cell priming by resident dendritic cells (DC). When analyzing 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 most part 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 conidiae than their splenic counterparts, which was highly dependent on Dectin-1. DCs in human BM could also phagocytose zymosan, which was dependent on β1-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, particularly in anti-fungal immunity. The ability of BM-resident DCs to boost neutrophil formation is relevant from a clinical perspective and contributes to our understanding of the increased susceptibility for fungal infections following BM damage.
Original language | English |
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Article number | 55 |
Number of pages | 18 |
Journal | Cells |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2022 |
Externally published | Yes |
Keywords
- Aged
- Aged, 80 and over
- Animals
- Antigens, Fungal/immunology
- Bone Marrow Cells/immunology
- Dendritic Cells/immunology
- Gene Expression Profiling
- Gene Expression Regulation
- Granulocyte Colony-Stimulating Factor/metabolism
- Humans
- Inflammation/pathology
- Lectins, C-Type/genetics
- Macrophage-1 Antigen/metabolism
- Mice, Inbred C57BL
- Middle Aged
- Neutrophils/immunology
- RNA, Messenger/genetics
- Zymosan/metabolism
- COLONY-STIMULATING FACTOR
- C/EBP-BETA
- RECOGNITION
- DECTIN-1
- TRANSPLANTATION
- hematopoiesis
- fungal infection
- dendritic cells
- granulopoiesis
- HEMATOPOIETIC STEM-CELLS
- G-CSF
- GRANULOCYTE
- bone marrow
- BETA-GLUCAN RECEPTOR
- dectin-1
- zymosan
- CLINICAL-PRACTICE