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

doi:10.1371/journal.pbio.1001658

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 journal › Article › peer-review

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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 language	English
Article number	e1001658
Pages (from-to)	1-18
Number of pages	18
Journal	PLoS Biology
Volume	11
Issue number	9
DOIs	https://doi.org/10.1371/journal.pbio.1001658
Publication status	Published - 17 Sept 2013

Bibliographical note

Acknowledgments: We express our gratitude to the “Unité Hospitalo-Universitaire d'expérimentation animale” technical platforms of IFR143. We would like also to thank Dr. A. Zimmer.

Funding: NR was supported by a fellowship from the MENRT (France). This work was financed by research grants from the Wellcome Trust (GDB), Sidaction, Cluster 10 of Infectiology, and Cayla-InvivoGen. BC's laboratory is supported by grant no. 3100-138422 from the Swiss Science Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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10.1371/journal.pbio.1001658Licence: CC BY

Dectin-1 Is Essential for Reverse Transcytosis of Glycosylated SIgA-Antigen Complexes by Intestinal M Cells
© 2013 Rochereau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Final published version, 2.59 MBLicence: CC BY

Cite this

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

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.",

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note = "Acknowledgments: We express our gratitude to the “Unit{\'e} Hospitalo-Universitaire d'exp{\'e}rimentation animale” technical platforms of IFR143. We would like also to thank Dr. A. Zimmer. Funding: NR was supported by a fellowship from the MENRT (France). This work was financed by research grants from the Wellcome Trust (GDB), Sidaction, Cluster 10 of Infectiology, and Cayla-InvivoGen. BC's laboratory is supported by grant no. 3100-138422 from the Swiss Science Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

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AU - Paul, Stéphane

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

Abstract

Bibliographical note

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

Abstract

Bibliographical note

UN SDGs

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