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Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells
Abstract
Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens. It is unclear how virus particles are cleared from afferent lymph and presented to cognate B cells to induce antibody responses. Here we identify a population of CD11b+CD169+MHCII+ macrophages on the floor of the subcapsular sinus (SCS) and in the medulla of lymph nodes that capture viral particles within minutes after subcutaneous injection. Macrophages in the SCS translocated surface-bound viral particles across the SCS floor and presented them to migrating B cells in the underlying follicles. Selective depletion of these macrophages compromised local viral retention, exacerbated viraemia of the host, and impaired local B-cell activation. These findings indicate that CD169+ macrophages have a dual physiological function. They act as innate 'flypaper' by preventing the systemic spread of lymph-borne pathogens and as critical gatekeepers at the lymph-tissue interface that facilitate the recognition of particulate antigens by B cells and initiate humoral immune responses.
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“These macrophages can capture larger molecules, viruses, and bacteria (89, 90) and are capable of mounting a protective immune response even in the absence of antigen-presenting DCs (91).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [90]
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Metadata
- Authors
- Junt, T., Moseman, E. A., Iannacone, M., Massberg, S., Lang, P. A., Boes, M., Fink, K., Henrickson, S. E., Shayakhmetov, D. M., Di Paolo, N. C., van Rooijen, N., Mempel, T. R., Whelan, S. P., & von Andrian, U. H.
- Affiliations
- Harvard University (US)
- University Hospital Zurich (CH)
- Brigham and Women's Hospital (US)
- Novartis Institute For Tropical Diseases (SG)
- University of Washington (US)
- Vrije Universiteit Amsterdam (NL)
- Corresponding author
- von Andrian, Ulrich H.
- ORCID
- Venue
- Nature
- Published
- 2007-10-14
- Volume
- 450
- Issue
- 7166
- Pages
- 110-114
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2019206924
- Cited by
- 846
- References
- 29
- Citations by year
- 2026: 21 · 2025: 38 · 2024: 37 · 2023: 34 · 2022: 35 · 2021: 55 · 2020: 46 · 2019: 49 · 2018: 53 · 2017: 53 · 2016: 46 · 2015: 53 · 2014: 46 · 2013: 38 · 2012: 66
- FWCI
- 17.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007753)
- National Institute of Allergy and Infectious Diseases (R01AI059371)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- subcapsular sinus macrophages, lymph node macrophages, CD169+ macrophages, viral clearance, B cell activation, antigen presentation, afferent lymph, humoral immune response, viremia, macrophage depletion
- MeSH terms
- Animals, Antibody Formation, B-Lymphocytes, Cell Line, Lymph, Lymph Nodes, Macrophages, Membrane Glycoproteins, Mice, Inbred C57BL, Receptors, Immunologic, Vesiculovirus, CD11b Antigen, Mice, Sialic Acid Binding Ig-like Lectin 1
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