TLR2 activation by proteosomes promotes uptake of particulate vaccines at mucosal surfaces

被引:34
作者
Chabot, Sophie M.
Chernin, Tyler S.
Shawi, May
Wagner, Jessica
Farrant, Stephanie
Burt, David S.
Cyr, Sonya
Neutra, Marian R.
机构
[1] GlaxoSmithKline Biol N Amer, Laval, PQ H7V 3S8, Canada
[2] Harvard Univ, Sch Med,GI Cell Biol Lab, Dept Pediat, Childrens Hosp, Boston, MA 02115 USA
[3] Harvard Digest Dis Ctr, Boston, MA 02115 USA
关键词
dendritic cells; mucosa; adjuvant;
D O I
10.1016/j.vaccine.2007.05.029
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 MIP3 alpha from Caco-2 epithelial cells in vitro. In HEK cells, proteosome-mediated MIP3 alpha 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. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5348 / 5358
页数:11
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