title: TLR2 activation by proteosomes promotes uptake of particulate vaccines at mucosal surfaces.
abstract: Proteosome-based vaccines have TLR2-based adjuvant activity and show promise for mucosal immunization. We examined the effects of proteosomes on mucosal uptake in Peyer's patches in vivo. Proteosomes accelerated transepithelial transport of microparticles by M cells and induced migration of dendritic cells (DCs) into the follicle-associated epithelium (FAE); both effects were dependent on TLR2. Proteosomes induced the release of the DC-attracting chemokine MIP3alpha from Caco-2 epithelial cells in vitro. In HEK cells, proteosome-mediated MIP3alpha release was dependent on TLR2 expression and matrix metalloproteinase activation. Thus, TLR2 activation by proteosomes may promote mucosal uptake of particulate vaccines, and this may contribute to their adjuvanticity.
authors.affiliation: Harvard Medical School, Department of Pediatrics, GI Cell Biology Laboratory, Children's Hospital Boston and Harvard Digestive Diseases Center, 300 Longwood Avenue, Boston, MA 02115, USA. sophie.chabot@childrens.harvard.edu
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Chabot
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Chernin
authors.forename: May
authors.initials: M
authors.lastname: Shawi
authors.forename: Jessica
authors.initials: J
authors.lastname: Wagner
authors.forename: Stephanie
authors.initials: S
authors.lastname: Farrant
authors.forename: David S
authors.initials: DS
authors.lastname: Burt
authors.forename: Sonya
authors.initials: S
authors.lastname: Cyr
authors.forename: Marian R
authors.initials: MR
authors.lastname: Neutra
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D023421:Models, Animal; D010581:Peyer's Patches / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
chemical_list: D001428:Bacterial Vaccines; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D051195:Toll-Like Receptor 2; D046988:Proteasome Endopeptidase Complex