CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice
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 t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/78873 |
| _version_ | 1817975788418367488 |
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| author | Jamie Moore-Fried Mahinder Paul Zhixin Jing David Fooksman Gregoire Lauvau |
| author_facet | Jamie Moore-Fried Mahinder Paul Zhixin Jing David Fooksman Gregoire Lauvau |
| author_sort | Jamie Moore-Fried |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-04-13T21:53:59Z |
| format | Article |
| id | doaj.art-aa653634f5574e27a503e5410d73b946 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-13T21:53:59Z |
| publishDate | 2022-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-aa653634f5574e27a503e5410d73b9462022-12-22T02:28:19ZengeLife Sciences Publications LtdeLife2050-084X2022-10-011110.7554/eLife.78873CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected miceJamie Moore-Fried0Mahinder Paul1Zhixin Jing2David Fooksman3Gregoire Lauvau4https://orcid.org/0000-0002-3050-2664Albert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, United StatesAlbert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, United StatesAlbert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, United States; Albert Einstein College of Medicine, Department of Pathology, New York, United StatesAlbert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, United States; Albert Einstein College of Medicine, Department of Pathology, New York, United StatesAlbert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, United StatesPlasmacytoid 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 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.https://elifesciences.org/articles/78873plasmacytoid dendritic cellCD169+ macrophagesevere malariatype I interferonintravital imagingbone marrow |
| spellingShingle | Jamie Moore-Fried Mahinder Paul Zhixin Jing David Fooksman Gregoire Lauvau CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice eLife plasmacytoid dendritic cell CD169+ macrophage severe malaria type I interferon intravital imaging bone marrow |
| title | CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice |
| title_full | CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice |
| title_fullStr | CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice |
| title_full_unstemmed | CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice |
| title_short | CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice |
| title_sort | cd169 macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria infected mice |
| topic | plasmacytoid dendritic cell CD169+ macrophage severe malaria type I interferon intravital imaging bone marrow |
| url | https://elifesciences.org/articles/78873 |
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