Clearance of influenza virus from the lung depends on migratory langerin+CD11b- but not plasmacytoid dendritic cells.
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.
GeurtsvanKessel
Corine H
CH
Department of Pulmonary Medicine, Erasmus University Medical Centre Rotterdam, 3015 GE Rotterdam, Netherlands.
Willart
Monique A M
MA
van Rijt
Leonie S
LS
Muskens
Femke
F
Kool
Mirjam
M
Baas
Chantal
C
Thielemans
Kris
K
Bennett
Clare
C
Clausen
Björn E
BE
Hoogsteden
Henk C
HC
Osterhaus
Albert D M E
AD
Rimmelzwaan
Guus F
GF
Lambrecht
Bart N
BN
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology*; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004285:Dogs; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008297:Male; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology / Q000821:virology; D014132:Trachea / Q000276:immunology / Q000821:virology
D000914:Antibodies, Viral; D000954:Antigens, Surface; D039481:CD11b Antigen; D039521:CD11c Antigen; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C498497:Cd207 protein, mouse; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D019590:Nucleocapsid Proteins