Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells

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dc.contributor.author Lam, Jennifer S. en_US
dc.contributor.author Huang, Haibin en_US
dc.contributor.author Levitz, Stuart M. en_US
dc.date.accessioned 2012-01-09T21:00:18Z
dc.date.available 2012-01-09T21:00:18Z
dc.date.issued 2007-10-10 en_US
dc.identifier.citation Lam, Jennifer S., Haibin Huang, Stuart M. Levitz. "Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells" PLoS ONE 2(10):e1009. (2007) en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/2967
dc.description.abstract BACKGROUND. An experimental approach for improving vaccine efficacy involves targeting antigens to mannose receptors (MRs) on dendritic cells (DCs) and other professional antigen presenting cells. Previously, we demonstrated that mannosylated Pichia pastoris-derived recombinant proteins exhibited increased immunogenicity compared to proteins lacking mannosylation. In order to gain insight into the mechanisms responsible for this observation, the present study examined the cellular uptake of the mannosylated and deglycosylated recombinant proteins. METHODOLOGY/PRINCIPAL FINDINGS. Utilizing transfected cell lines, roles for the macrophage mannose receptor (MMR, CD206) and DC-SIGN (CD209) in the recognition of the mannosylated, but not deglycosylated, antigens were demonstrated. The uptake of mannosylated antigens into murine bone marrow-derived DCs (BMDCs) was inhibited by yeast mannans (YMs), suggesting a mannose-specific C-type lectin receptor-dependent process, while the uptake of deglycosylated antigens remained unaffected. In particular, antigens with both N-linked and extensive O-linked mannosylation showed the highest binding and uptake by BMDCs. Finally, confocal microscopy studies revealed that both mannosylated and deglycosylated P. pastoris-derived recombinant proteins localized in MHC class II+ compartments within BMDCs. CONCLUSIONS/SIGNIFICANCE. Taken together with our previous results, these data suggest that increased uptake by mannose-specific C-type lectin receptors is the major mechanism responsible for the enhanced antigenicity seen with mannosylated proteins. These findings have important implications for vaccine design and contribute to our understanding of how glycosylation affects the immune response to eukaryotic pathogens. en_US
dc.description.sponsorship National Institutes of Health (RO1 AI25780, RO1 AI37532) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.title Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0001009 en_US
dc.identifier.pubmedid 17925857 en_US
dc.identifier.pmcid 1995759 en_US

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