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Journal of Clinical Investigation (1)
The Journal of Experimental Medicine (1)
Lambrecht, Bart N. (2)
Baas, Chantal (1)
Bennett, Clare (1)
Clausen, Björn E. (1)
Coyle, Anthony J. (1)
De Veerman, Marijke (1)
GeurtsvanKessel, Corine H. (1)
Gutierrez-Ramos, Jose-Carlos (1)
Hoogsteden, Henk C. (1)
Kool, Mirjam (1)
Muskens, Femke (1)
Osterhaus, Albert D.M.E. (1)
Pauwels, Romain A. (1)
Rimmelzwaan, Guus F. (1)
Willart, Monique A.M. (1)
van Rijt, Leonie S. (1)
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Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation
De Veerman, Marijke
Coyle, Anthony J.
Pauwels, Romain A.
Journal of Clinical Investigation
The aim of this study was to investigate whether dendritic cells (DCs) can induce sensitization to aeroallergen in a mouse model of allergic asthma. Ovalbumin-pulsed (OVA-pulsed) or unpulsed myeloid DCs that were injected into the airways of naive mice migrated into the mediastinal lymph nodes. When challenged 2 weeks later with an aerosol of OVA, activated CD4 and CD8 lymphocytes, eosinophils, and neutrophils were recruited to the lungs of actively immunized mice. These CD4+ lymphocytes produced predominantly IL-4 and IL-5 but also IFN-γ, whereas CD8+ lymphocytes produced predominantly IFN-γ. Histological analysis revealed perivascular and peribronchial eosinophilic infiltrates and goblet cell hyperplasia. Studies in IL-4–/– and CD28–/– mice revealed that production of IL-4 by host cells and provision of costimulation to T cells by DCs were critical for inducing the response. Lung CD4+ T cells strongly expressed the Th2 marker T1/ST2, and signaling through this molecule via a ligand expressed on DCs was essential for the establishment of airway eosinophilia. These data demonstrate that DCs in the airways induce sensitization to inhaled antigen and that molecules expressed on the surface of these cells are critical for the development of Th2-dependent airway eosinophilia.
Clearance of influenza virus from the lung depends on migratory langerin+CD11b− but not plasmacytoid dendritic cells
GeurtsvanKessel, Corine H.
Willart, Monique A.M.
van Rijt, Leonie S.
Clausen, Björn E.
Hoogsteden, Henk C.
Osterhaus, Albert D.M.E.
Rimmelzwaan, Guus F.
The Journal of Experimental Medicine
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−CD8α+ DCs presented to CD8 cells, and migratory CD11b−CD8α− 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.
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