title: From secretome analysis to immunology: chitosan induces major alterations in the activation of dendritic cells via a TLR4-dependent mechanism.
abstract: Dendritic cells are known to be activated by a wide range of microbial products, leading to cytokine production and increased levels of membrane markers such as major histocompatibility complex class II molecules. Such activated dendritic cells possess the capacity to activate naïve T cells. In the present study we demonstrated that immature dendritic cells secrete both the YM1 lectin and lipocalin-2. By testing the ligands of these two proteins, chitosan and siderophores, respectively, we also demonstrated that chitosan, a degradation product of various fungal and protozoal cell walls, induces an activation of dendritic cells at the membrane level, as shown by the up-regulation of membrane proteins such as class II molecules, CD80 and CD86 via a TLR4-dependent mechanism, but is not able to induce cytokine production. This led to the production of activated dendritic cells unable to stimulate T cells. However, costimulation with other microbial products overcame this partial activation and restored the capacity of these activated dendritic cells to stimulate T cells. In addition, successive stimulation with chitosan and then by lipopolysaccharide induced a dose-dependent change in the cytokinic IL-12/IL-10 balance produced by the dendritic cells.
authors.affiliation: double daggerINSERM U823 Analytical Immunology of Chronic Pathologies, Institut Albert Bonniot, BP170, 38042 Grenoble, France and Université Joseph Fourier, F-38041 Grenoble, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Villiers
authors.forename: Mireille
authors.initials: M
authors.lastname: Chevallet
authors.forename: Hélène
authors.initials: H
authors.lastname: Diemer
authors.forename: Rachel
authors.initials: R
authors.lastname: Couderc
authors.forename: Heidi
authors.initials: H
authors.lastname: Freitas
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
authors.forename: Thierry
authors.initials: T
authors.lastname: Rabilloud
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D048271:Chitosan / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D007525:Isoelectric Focusing; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D010455:Peptides; D051197:Toll-Like Receptor 4; D048271:Chitosan