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- Title
CD169<sup>+ </sup>macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice.
- Authors
Moore-Fried, Jamie; Paul, Mahinder; Zhixin Jing; Fooksman, David; Lauvau, Gregoire
- Abstract
Plasmacytoid dendritic cells (pDCs) are the most potent producer of type I interferon (IFN), but how pDC is primed in vivo is poorly defined. Using a mouse model of severe malaria, we have previously established that upon priming by CD169+ macrophages (MPs), pDC initiates type I IFN-I secretion in the bone marrow (BM) of infected mice via cell-intrinsic TLR7 sensing and cellextrinsic STING sensing. Herein we show that CD169+ MP and TLR7 sensing are both required for pDC arrest during priming, suggesting CD169+ MP are the source of TLR7 ligands. We establish that TLR7 sensing in pDC and chemotaxis are both required for pDC arrest and functional communication with CD169+ MP in the BM. Lastly, we demonstrate that STING sensing in CD169+ MP control pDC initiation of type I IFN production while also regulating pDC clustering and retention/egress from the BM. Collectively, these results link pDC acquisition of type I IFN-secreting capacity with changes in their motility, homing and interactions with CD169+ MP during infection. Thus, targeting this cellular interaction may help modulate type I IFN to improve outcomes of microbial infections and autoimmune diseases.
- Subjects
DENDRITIC cells; BONE marrow; TYPE I interferons; ARREST; MICE; MARIJUANA growing
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.78873