Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells

Tobias Junt, E. Ashley Moseman, Matteo Iannacone, Steffen Massberg, Philipp A. Lang, Marianne Boes, Katja Fink, Sarah E. Henrickson, Dmitry M. Shayakhmetov, Nelson C. Di Paolo, Nico Van Rooijen, Thorsten R. Mempel, Sean P. Whelan, Ulrich H. Von Andrian

Research output: Contribution to journalArticle

497 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)110-114
Number of pages5
JournalNature
Volume450
Issue number7166
DOIs
Publication statusPublished - Nov 1 2007

Fingerprint

Lymph
Antiviral Agents
B-Lymphocytes
Lymph Nodes
Macrophages
Virion
Viruses
Antigens
Viremia
Adaptive Immunity
Subcutaneous Injections
Humoral Immunity
Antibody Formation
Population

ASJC Scopus subject areas

  • General

Cite this

Junt, T., Moseman, E. A., Iannacone, M., Massberg, S., Lang, P. A., Boes, M., ... Von Andrian, U. H. (2007). Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature, 450(7166), 110-114. https://doi.org/10.1038/nature06287

Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. / Junt, Tobias; Moseman, E. Ashley; Iannacone, Matteo; Massberg, Steffen; Lang, Philipp A.; Boes, Marianne; Fink, Katja; Henrickson, Sarah E.; Shayakhmetov, Dmitry M.; Di Paolo, Nelson C.; Van Rooijen, Nico; Mempel, Thorsten R.; Whelan, Sean P.; Von Andrian, Ulrich H.

In: Nature, Vol. 450, No. 7166, 01.11.2007, p. 110-114.

Research output: Contribution to journalArticle

Junt, T, Moseman, EA, Iannacone, M, Massberg, S, Lang, PA, Boes, M, Fink, K, Henrickson, SE, Shayakhmetov, DM, Di Paolo, NC, Van Rooijen, N, Mempel, TR, Whelan, SP & Von Andrian, UH 2007, 'Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells', Nature, vol. 450, no. 7166, pp. 110-114. https://doi.org/10.1038/nature06287
Junt, Tobias ; Moseman, E. Ashley ; Iannacone, Matteo ; Massberg, Steffen ; Lang, Philipp A. ; Boes, Marianne ; Fink, Katja ; Henrickson, Sarah E. ; Shayakhmetov, Dmitry M. ; Di Paolo, Nelson C. ; Van Rooijen, Nico ; Mempel, Thorsten R. ; Whelan, Sean P. ; Von Andrian, Ulrich H. / Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. In: Nature. 2007 ; Vol. 450, No. 7166. pp. 110-114.
@article{e342f2cc3cb24858be48841b9fcd2859,
title = "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.",
author = "Tobias Junt and Moseman, {E. Ashley} and Matteo Iannacone and Steffen Massberg and Lang, {Philipp A.} and Marianne Boes and Katja Fink and Henrickson, {Sarah E.} and Shayakhmetov, {Dmitry M.} and {Di Paolo}, {Nelson C.} and {Van Rooijen}, Nico and Mempel, {Thorsten R.} and Whelan, {Sean P.} and {Von Andrian}, {Ulrich H.}",
year = "2007",
month = "11",
day = "1",
doi = "10.1038/nature06287",
language = "English",
volume = "450",
pages = "110--114",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7166",

}

TY - JOUR

T1 - Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells

AU - Junt, Tobias

AU - Moseman, E. Ashley

AU - Iannacone, Matteo

AU - Massberg, Steffen

AU - Lang, Philipp A.

AU - Boes, Marianne

AU - Fink, Katja

AU - Henrickson, Sarah E.

AU - Shayakhmetov, Dmitry M.

AU - Di Paolo, Nelson C.

AU - Van Rooijen, Nico

AU - Mempel, Thorsten R.

AU - Whelan, Sean P.

AU - Von Andrian, Ulrich H.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=35948935059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35948935059&partnerID=8YFLogxK

U2 - 10.1038/nature06287

DO - 10.1038/nature06287

M3 - Article

C2 - 17934446

AN - SCOPUS:35948935059

VL - 450

SP - 110

EP - 114

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7166

ER -