The adjuvanticity of a mannosylated antigen reveals TLR4 functionality essential for subset specialization and functional maturation of mouse dendritic cells

Sheng, K, Kalkanidis, M, Pouniotis, D, Wright, M, Pietersz, G and Apostolopoulos, V 2008, 'The adjuvanticity of a mannosylated antigen reveals TLR4 functionality essential for subset specialization and functional maturation of mouse dendritic cells', Journal of Immunology, vol. 15, no. 4, pp. 2455-2464.


Document type: Journal Article
Collection: Journal Articles

Title The adjuvanticity of a mannosylated antigen reveals TLR4 functionality essential for subset specialization and functional maturation of mouse dendritic cells
Author(s) Sheng, K
Kalkanidis, M
Pouniotis, D
Wright, M
Pietersz, G
Apostolopoulos, V
Year 2008
Journal name Journal of Immunology
Volume number 15
Issue number 4
Start page 2455
End page 2464
Total pages 10
Publisher American Association of Immunologists
Abstract The evidence that dendritic cell (DC) subsets produce differential cytokines in response to specific TLR stimulation is robust. However, the role of TLR stimulation in Ag presentation and phenotypic maturation among DC subsets is not clear. Through the adjuvanticity of a novel mannosylated Ag, mannosylated dendrimer OVA (MDO), as a pathogen-associated molecular pattern Ag, we characterized the functionality of GM-CSF/IL-4-cultured bone marrow DC and Flt3 ligand (Flt3-L) DC subsets by Ag presentation and maturation assays. It was demonstrated that both bone marrow DCs and Flt3-L DCs bound, processed, and presented MDO effectively. However, while Flt3-L CD24high (conventional CD8+ equivalent) and CD11bhigh (CD8 - equivalent) DCs were adept at MDO processing by MHC class I and II pathways, respectively, CD45RA+ plasmacytoid DCs presented MDO poorly to T cells. Successful MDO presentation was largely dependent on competent TLR4 for Ag localization and morphological/phenotypic maturation of DC subsets, despite the indirect interaction of MDO with TLR4. Furthermore, Toll/IL-1 receptor-domain-containing adaptor-inducing IFN-ß, but not MyD88, as a TLR4 signaling modulator was indispensable for MDO-induced DC maturation and Ag presentation. Taken together, our findings suggest that DC subsets differentially respond to a pathogenassociated molecular pattern-associated Ag depending on the intrinsic programming and TLRs expressed. Optimal functionality of DC subsets in Ag presentation necessitates concomitant TLR signaling critical for efficient Ag localization and processing.
ISSN 0022-1767
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