Dectin-1 is essential for reverse transcytosis of glycosylated SIgA-antigen complexes by intestinal M cells.
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.
GIMAP/EA3064, INSERM CIE3 Vaccinology, Université de Lyon, Saint-Etienne, France.
Nicolas
N
Rochereau
Daniel
D
Drocourt
Eric
E
Perouzel
Vincent
V
Pavot
Pierre
P
Redelinghuys
Gordon D
GD
Brown
Gerard
G
Tiraby
Xavier
X
Roblin
Bernard
B
Verrier
Christian
C
Genin
Blaise
B
Corthésy
Stéphane
S
Paul
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016466:CHO Cells; D000073883:CX3C Chemokine Receptor 1; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006031:Glycosylation; D016655:HIV Core Protein p24 / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D037102:Lectins / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D057900:Transcytosis / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000073883:CX3C Chemokine Receptor 1; D015815:Cell Adhesion Molecules; D016655:HIV Core Protein p24; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D037102:Lectins; D037181:Lectins, C-Type; D019158:N-Acetylneuraminic Acid; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1; C095235:CX3CR1 protein, human; C114531:SIGLEC5 protein, human; C042441:glycosylated IgA