Abstract
Although dendritic cells (DCs) play an important role in mediating protection against influenza virus, the precise role of lung DC subsets, such as CD11b- and CD11b+ conventional DCs or plasmacytoid DCs (pDCs), in different lung compartments is currently unknown. Early after intranasal infection, tracheal CD11b-CD11chi DCs migrated to the mediastinal lymph nodes (MLNs), acquiring co-stimulatory molecules in the process. This emigration from the lung was followed by an accumulation of CD11b+CD11chi DCs in the trachea and lung interstitium. In the MLNs, the CD11b+ DCs contained abundant viral nucleoprotein (NP), but these cells failed to present antigen to CD4 or CD8 T cells, whereas resident CD11b-CD8+ DCs presented to CD8 cells, and migratory CD11b-CD8- DCs presented to CD4 and CD8 T cells. When lung CD11chi DCs and macrophages or langerin+CD11b-CD11chi DCs were depleted using either CD11c-diphtheria toxin receptor (DTR) or langerin-DTR mice, the development of virus-specific CD8+ T cells was severely delayed, which correlated with increased clinical severity and a delayed viral clearance. 120G8+ CD11cint pDCs also accumulated in the lung and LNs carrying viral NP, but in their absence, there was no effect on viral clearance or clinical severity. Rather, in pDC-depleted mice, there was a reduction in antiviral antibody production after lung clearance of the virus. This suggests that multiple DCs are endowed with different tasks in mediating protection against influenza virus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Viral / immunology
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Antibody Formation / genetics
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Antigen Presentation / genetics
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Antigens, Surface / genetics
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Antigens, Surface / immunology*
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CD11b Antigen / genetics
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CD11b Antigen / immunology*
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CD11c Antigen / genetics
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CD11c Antigen / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / virology
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CD8 Antigens / genetics
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CD8 Antigens / immunology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / virology
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Cell Movement / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / virology
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Dogs
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Female
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / immunology
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology*
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Lung / immunology*
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Lung / virology
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Lymph Nodes / immunology
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Lymph Nodes / virology
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Male
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Mannose-Binding Lectins / genetics
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Mannose-Binding Lectins / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Nucleocapsid Proteins / immunology
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Orthomyxoviridae / immunology*
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Orthomyxoviridae Infections / genetics
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Orthomyxoviridae Infections / immunology*
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Plasma Cells / immunology
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Plasma Cells / virology
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Trachea / immunology
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Trachea / virology
Substances
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Antibodies, Viral
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Antigens, Surface
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CD11b Antigen
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CD11c Antigen
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CD8 Antigens
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CD8 antigen, alpha chain
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Cd207 protein, mouse
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Hbegf protein, mouse
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins
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Lectins, C-Type
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Mannose-Binding Lectins
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Nucleocapsid Proteins