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

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.

Immunoglobulin A antibodies against ricin A and B subunits protect epithelial cells from ricin intoxication.

Epithelial cells of the respiratory and gastrointestinal tracts are extremely vulnerable to the cytotoxic effects of ricin, a Shiga-like toxin with ribosome-inactivating properties. While mucosal immunity to ricin correlates with secretory immunoglobulin A (IgA) antibody levels in vivo, the potential of IgA to protect epithelial cells from ricin in vitro has not been examined due to the unavailability of well-defined antitoxin IgA antibodies. Here we report the characterization of four monoclonal IgA antibodies (IgA MAbs) produced from the Peyer's patches and mesenteric lymph nodes of BALB/c mice immunized intragastrically with ricin toxoid.

TLRs regulate the gatekeeping functions of the intestinal follicle-associated epithelium.

Initiation of adaptive mucosal immunity occurs in organized mucosal lymphoid tissues such as Peyer's patches of the small intestine. Mucosal lymphoid follicles are covered by a specialized follicle-associated epithelium (FAE) that contains M cells, which mediate uptake and transepithelial transport of luminal Ags. FAE cells also produce chemokines that attract Ag-presenting dendritic cells (DCs).

Ricin induces IL-8 secretion from human monocyte/macrophages by activating the p38 MAP kinase pathway.

Polymorphonuclear cell (PMN) infiltration is a hallmark of ricin-induced mucosal inflammation, yet the cellular processes involved in initiating this reaction remain undefined. In this study we report that ricin stimulates the human monocyte/macrophages cell line 28SC to secrete IL-8, a potent PMN chemoattractant. IL-8 release in response to ricin was both dose- and time-dependent.

Oligosaccharide side chains on human secretory IgA serve as receptors for ricin.

Secretory IgA (sIgA) Abs are polymeric Igs comprised of two or more IgA monomers joined together at their C termini and covalently associated with a 70-kDa glycoprotein called secretory component. As the predominant Ig type in gastrointestinal sections, sIgA Abs are centrally important in adaptive immunity to enteropathogenic bacteria, viruses, and toxins. In this study, we demonstrate that sIgA Abs may also function in innate defense against ricin, a naturally occurring, galactose-specific plant lectin with extremely potent shiga toxin-like enzymatic activity.