Essential role of TOSO/FAIM3 in intestinal IgM reverse transcytosis.

Nicolas Rochereau,Martin Killian,Stéphane Paul,Rémi Gayet,Gilles Biolley,Eva Michaud,Xavier Roblin,Roman Goguyer-Deschaumes,Blaise Corthésy,Louis Waeckel

doi:10.1016/j.celrep.2021.110006

Abstract

Secretory immunoglobulin A (SIgA) can travel to and from the lumen and transport antigen to subepithelial cells. However, IgM can also multimerize into functional secretory component-bound immunoglobulin. While it is already known that both SIgA and SIgM undergo transcytosis to be secreted at the mucosal surface, only SIgA has been shown to perform retrotranscytosis through microfold cells (M cells) of the Peyer's patch. Here, we investigate whether SIgM could also be taken up by M cells via retrotranscytosis. This transport involves FcμR binding at the apical membrane of M cells. We then demonstrate that SIgM can be exploited by SIgM-p24 (HIV-capsid protein) complexes during immunization in the nasal- or gut-associated lymphoid tissue (NALT or GALT), conferring efficient immune responses against p24. Our data demonstrate a mucosal function of SIgM, which could play a role in the regulation of mucosal immunity.

Highlights

The concept of local or mucosal immunity has expanded dramatically over the past few decades
We showed that secreted IgM (SIgM)-bound p24 HIV-1 antigen was taken up by microfold cells (M cells) in vivo in both murine Gut-associated lymphoid tissue (GALT) and nasal-associated lymphoid tissue (NALT), allowing for the induction of a strong p24-specific immunity
Specificity of IgM reverse transcytosis was further confirmed in vivo after fluorescent IgM administration in ligated murine intestinal loop experiments (Figure 1C)

Summary

Introduction

The concept of local or mucosal immunity has expanded dramatically over the past few decades. Evidence has emerged indicating that SIgA promotes the uptake and delivery of antigens from the intestinal lumen to dendritic cell (DC) subsets located in the GALT It thusly influences inflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. Our and previous data have shown that SIgA selectively binds Dectin-1 and SIGLEC-5 (sialic acidbinding immunoglobulin-like lectin 5) receptors at the apical membrane of Peyer’s patches (PPs) in M cells. This triggers SIgA transport across the epithelium toward underlying DCs of the subepithelial dome (SED) region, inducing their maturation and migration to the interfollicular areas (Rochereau et al, 2013a). Considerable emphasis has been devoted to the role of IgA because of its relative abundance in digestive tract secretions, mucosal functions of SIgM have been comparatively neglected

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Conclusion