Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Viral / blood
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Antigen Presentation
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism*
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Cell Movement
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Cells, Cultured
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Clodronic Acid / administration & dosage
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Dendrimers / administration & dosage
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / pathology
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Dendritic Cells / virology
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Endocytosis* / drug effects
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Endocytosis* / genetics
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Immunity, Humoral / drug effects
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Immunity, Humoral / genetics
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Immunoglobulin Heavy Chains / genetics
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Immunotherapy, Active
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Influenza A virus / immunology*
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Influenza A virus / pathogenicity
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Influenza Vaccines / administration & dosage
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism*
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Lymph Nodes / pathology
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Lymph Nodes / virology
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Macrophages / drug effects
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Macrophages / immunology
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Macrophages / metabolism*
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Macrophages / pathology
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Macrophages / virology
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Mannose-Binding Lectin / genetics
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Mannose-Binding Lectin / metabolism
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Mice
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Mice, Knockout
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Mice, Transgenic
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Microscopy, Fluorescence, Multiphoton
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
Substances
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Antibodies, Viral
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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Dendrimers
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Immunoglobulin Heavy Chains
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Influenza Vaccines
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Lectins, C-Type
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Mannose-Binding Lectin
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Receptors, Cell Surface
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Clodronic Acid