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- Title
Clearance of influenza virus from the lung depends on migratory langerin+CD11b- but not plasmacytoid dendritic cells.
- Authors
GeurtsvanKessel, Corine H; Willart, Monique A M; van Rijt, Leonie S; Muskens, Femke; Kool, Mirjam; Baas, Chantal; Thielemans, Kris; Bennett, Clare; Clausen, Björn E; Hoogsteden, Henk C; Osterhaus, Albert D M E; Rimmelzwaan, Guus F; Lambrecht, Bart N
- 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
The Journal of experimental medicine, 2008, Vol 205, Issue 7, p1621
- ISSN
1540-9538
- Publication type
Journal Article
- DOI
10.1084/jem.20071365