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¹ Department of Pulmonary Medicine and ² Department of Virology, Erasmus University Medical Centre Rotterdam, 3015 GE Rotterdam, Netherlands
³ Department of Respiratory Diseases, University Hospital Ghent, 9000 Ghent, Belgium
⁴ Department of Physiology, Free University Brussels, 1090 Brussels, Belgium
⁵ Department of Cell Biology and Histology, University of Amsterdam, 1105 AZ Amsterdam, Netherlands

CORRESPONDENCE Bart N. Lambrecht: bart.lambrecht{at}ugent.be

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^–CD11c^hi 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⁺CD11c^hi 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 CD11c^hi DCs and macrophages or langerin⁺CD11b^–CD11c^hi 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⁺ CD11c^int 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.

G.F. Rimmelzwaan and B.N. Lambrecht contributed equally to this paper.

© 2008 GeurtsvanKessel et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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