Dectin-1 Is Essential for Reverse Transcytosis of Glycosylated SIgA-Antigen Complexes by Intestinal M Cells

Nicolas Rochereau, Daniel Drocourt, Eric Perouzel, Vincent Pavot, Pierre Redelinghuys, Gordon D. Brown, Gerard Tiraby, Xavier Roblin, Bernard Verrier, Christian Genin, Blaise Corthésy, Stéphane Paul*

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Intestinal microfold (M) cells possess a high transcytosis capacity and are able to transport a broad range of materials including particulate antigens, soluble macromolecules, and pathogens from the intestinal lumen to inductive sites of the mucosal immune system. M cells are also the primary pathway for delivery of secretory IgA (SIgA) to the gut-associated lymphoid tissue. However, although the consequences of SIgA uptake by M cells are now well known and described, the mechanisms whereby SIgA is selectively bound and taken up remain poorly understood. Here we first demonstrate that both the Cα1 region and glycosylation, more particularly sialic acid residues, are involved in M cell-mediated reverse transcytosis. Second, we found that SIgA is taken up by M cells via the Dectin-1 receptor, with the possible involvement of Siglec-5 acting as a co-receptor. Third, we establish that transcytosed SIgA is taken up by mucosal CX3CR1+ dendritic cells (DCs) via the DC-SIGN receptor. Fourth, we show that mucosal and systemic antibody responses against the HIV p24-SIgA complexes administered orally is strictly dependent on the expression of Dectin-1. Having deciphered the mechanisms leading to specific targeting of SIgA-based Ag complexes paves the way to the use of such a vehicle for mucosal vaccination against various infectious diseases.

Original languageEnglish
Article numbere1001658
Pages (from-to)1-18
Number of pages18
JournalPLoS Biology
Volume11
Issue number9
DOIs
Publication statusPublished - 17 Sep 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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  • Cite this

    Rochereau, N., Drocourt, D., Perouzel, E., Pavot, V., Redelinghuys, P., Brown, G. D., Tiraby, G., Roblin, X., Verrier, B., Genin, C., Corthésy, B., & Paul, S. (2013). Dectin-1 Is Essential for Reverse Transcytosis of Glycosylated SIgA-Antigen Complexes by Intestinal M Cells. PLoS Biology, 11(9), 1-18. [e1001658]. https://doi.org/10.1371/journal.pbio.1001658