Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes

Vaccines elicit neutralizing antibodies to protect organisms against viral infection. Carroll and colleagues show that medullary lymph node dendritic cells capture influenza virus via SIGN-R1 and are necessary for humoral antiviral immunity. A major pathway for B cell acquisition of lymph-borne part...

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Veröffentlicht in:Nature immunology 2010-05, Vol.11 (5), p.427-434
Hauptverfasser: Gonzalez, Santiago F, Lukacs-Kornek, Veronika, Kuligowski, Michael P, Pitcher, Lisa A, Degn, Søren E, Kim, Young-A, Cloninger, Mary J, Martinez-Pomares, Luisa, Gordon, Siamon, Turley, Shannon J, Carroll, Michael C
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container_end_page 434
container_issue 5
container_start_page 427
container_title Nature immunology
container_volume 11
creator Gonzalez, Santiago F
Lukacs-Kornek, Veronika
Kuligowski, Michael P
Pitcher, Lisa A
Degn, Søren E
Kim, Young-A
Cloninger, Mary J
Martinez-Pomares, Luisa
Gordon, Siamon
Turley, Shannon J
Carroll, Michael C
description Vaccines elicit neutralizing antibodies to protect organisms against viral infection. Carroll and colleagues show that medullary lymph node dendritic cells capture influenza virus via SIGN-R1 and are necessary for humoral antiviral immunity. A major pathway for B cell acquisition of lymph-borne particulate antigens relies on antigen capture by subcapsular sinus macrophages of the lymph node. Here we tested whether this mechanism is also important for humoral immunity to inactivated influenza virus. By multiple approaches, including multiphoton intravital imaging, we found that antigen capture by sinus-lining macrophages was important for limiting the systemic spread of virus but not for the generation of influenza-specific humoral immunity. Instead, we found that dendritic cells residing in the lymph node medulla use the lectin receptor SIGN-R1 to capture lymph-borne influenza virus and promote humoral immunity. Thus, our results have important implications for the generation of durable humoral immunity to viral pathogens through vaccination.
doi_str_mv 10.1038/ni.1856
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subjects 631/250/24
631/250/2504/133
631/250/255/1578
692/420/2780/2152/2153
Animals
Antibodies, Viral - blood
Antigen Presentation
Biomedical and Life Sciences
Biomedicine
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - immunology
Cell Adhesion Molecules - metabolism
Cell Movement
Cells, Cultured
Clodronic Acid - administration & dosage
Dendrimers - administration & dosage
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dendritic Cells - pathology
Dendritic Cells - virology
Endocytosis - drug effects
Endocytosis - genetics
Health aspects
Immunity, Humoral - drug effects
Immunity, Humoral - genetics
Immunoglobulin Heavy Chains - genetics
Immunology
Immunotherapy, Active
Infectious Diseases
Influenza A virus - immunology
Influenza A virus - pathogenicity
Influenza vaccines
Influenza Vaccines - administration & dosage
Influenza virus
Influenza viruses
Lectins, C-Type - genetics
Lectins, C-Type - immunology
Lectins, C-Type - metabolism
Lymph nodes
Lymph Nodes - pathology
Lymph Nodes - virology
Macrophages - drug effects
Macrophages - immunology
Macrophages - metabolism
Macrophages - pathology
Macrophages - virology
Mannose-Binding Lectin - genetics
Mannose-Binding Lectin - metabolism
Mice
Mice, Knockout
Mice, Transgenic
Microscopy, Fluorescence, Multiphoton
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - prevention & control
Pathogens
Physiological aspects
Receptors, Cell Surface - genetics
Receptors, Cell Surface - immunology
Receptors, Cell Surface - metabolism
title Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes
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