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-CD11chiDCs 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+CD11chiDCs 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-CD8α+DCs presented to CD8 cells, and migratory CD11b-CD8α-DCs presented to CD4 and CD8 T cells. When lung CD11chiDCs and macrophages or langerin+CD11b-CD11chiDCs were depleted using either CD11c - diphtheria toxin receptor (DTR) or langerin-DTR mice, the development of virus-specif c CD8+T cells was severely delayed, which correlated with increased clinical severity and a delayed viral clearance. 120G8+CD11cintpDCs 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.

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