title: Reduction of T-Helper Cell Responses to Recall Antigen Mediated by Codelivery with Peptidoglycanviathe Intestinal Nanomineral-Antigen Pathway.
abstract: Naturally occurring intestinal nanomineral particles constituently form in the mammalian gut and trap luminal protein and microbial components. These cargo loaded nanominerals are actively scavenged by M cells of intestinal immune follicles, such as Peyer's patches and are passed to antigen-presenting cells. Using peripheral blood mononuclear cell populations as anin vitromodel of nanomineral uptake and antigen presentation, we show that monocytes avidly phagocytose nanomineral particles bearing antigen and peptidoglycan (PGN), and that the presence of PGN within particles downregulates their cell surface MHC class II and upregulates programmed death receptor ligand 1. Nanomineral delivery of antigen suppresses antigen-specific CD4+T cell responses, an effect that is enhanced in the presence of PGN. Blocking the interleukin-10 receptor restores CD4+T cell responses to antigen codelivered with PGN in nanomineral form. Using human intestinal specimens, we have shown that thein vivonanomineral pathway operates in an interleukin-10 rich environment. Consequently, the delivery of a dual antigen-PGN cargo by endogenous nanomineralin vivois likely to be important in the establishment of intestinal tolerance, while their synthetic mimetics present a potential delivery system for therapeutic applications targeting the modulation of Peyer's patch T cell responses.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK; Medical Research Council, Department of Mineral Science and Technology, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Hewitt
authors.affiliation: Medical Research Council, Department of Mineral Science and Technology, Elsie Widdowson Laboratory , Cambridge , UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Medical Research Council, Department of Mineral Science and Technology, Elsie Widdowson Laboratory , Cambridge , UK.
authors.forename: Carolin T
authors.initials: CT
authors.lastname: Haas
authors.affiliation: Medical Research Council, Department of Mineral Science and Technology, Elsie Widdowson Laboratory , Cambridge , UK.
authors.forename: Laetitia C
authors.initials: LC
authors.lastname: Pele
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK; Medical Research Council, Department of Mineral Science and Technology, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Powell
keywords: IL-10; T cells; antigen-presenting cells; intestinal tolerance; nanomineral; peptidoglycan; programmed death receptor ligand 1