CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice
- Albert Einstein College of Medicine, United States
Abstract
Plasmacytoid dendritic cells (pDC) are the most potent producer of type I interferon (IFN), but how pDC are primed in vivo is poorly defined. Using a mouse model of severe malaria, we have previously established that upon priming by CD169+ macrophages (MP), pDC initiate type I IFN-I secretion in the bone marrow (BM) of infected mice via cell-intrinsic TLR7 sensing and cell-extrinsic 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all figures. There is no restriction of access.
Article and author information
Author details
Funding
NIAID (AI103666)
- David Fooksman
- Gregoire Lauvau
NIH (T32 GM7288 ; F31 HL147470)
- Jamie Moore-Fried
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was carried out in strict accordance with the recommendations by the animal use committee at the Albert Einstein College of Medicine under protocol number #20171113 and 00001375. The institution is accredited by the "American Association for the Use of Laboratory Animals" (DHEW Publication No. (NIH) 78-23, Revised 1978), and accepts as mandatory the NIH "Principles for the Use of Animals". All efforts were made to minimize suffering and provide humane treatment to the animals included in the study.
Copyright
© 2022, Moore-Fried et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice
eLife 11:e78873.
https://doi.org/10.7554/eLife.78873
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