title: Brucella β 1,2 cyclic glucan is an activator of human and mouse dendritic cells.
abstract: Bacterial cyclic glucans are glucose polymers that concentrate within the periplasm of alpha-proteobacteria. These molecules are necessary to maintain the homeostasis of the cell envelope by contributing to the osmolarity of Gram negative bacteria. Here, we demonstrate that Brucella β 1,2 cyclic glucans are potent activators of human and mouse dendritic cells. Dendritic cells activation by Brucella β 1,2 cyclic glucans requires TLR4, MyD88 and TRIF, but not CD14. The Brucella cyclic glucans showed neither toxicity nor immunogenicity compared to LPS and triggered antigen-specific CD8(+) T cell responses in vivo. These cyclic glucans also enhanced antigen-specific CD4(+) and CD8(+) T cell responses including cross-presentation by different human DC subsets. Brucella β 1,2 cyclic glucans increased the memory CD4(+) T cell responses of blood mononuclear cells exposed to recombinant fusion proteins composed of anti-CD40 antibody and antigens from both hepatitis C virus and Mycobacterium tuberculosis. Thus cyclic glucans represent a new class of adjuvants, which might contribute to the development of effective antimicrobial therapies.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University, UM2, Marseille, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Martirosyan
authors.forename: Camino
authors.initials: C
authors.lastname: Pérez-Gutierrez
authors.forename: Romain
authors.initials: R
authors.lastname: Banchereau
authors.forename: Hélène
authors.initials: H
authors.lastname: Dutartre
authors.forename: Patrick
authors.initials: P
authors.lastname: Lecine
authors.forename: Melissa
authors.initials: M
authors.lastname: Dullaers
authors.forename: Marielle
authors.initials: M
authors.lastname: Mello
authors.forename: Suzana Pinto
authors.initials: SP
authors.lastname: Salcedo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Muller
authors.forename: Lee
authors.initials: L
authors.lastname: Leserman
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.forename: Sandy
authors.initials: S
authors.lastname: Zurawski
authors.forename: Edgardo
authors.initials: E
authors.lastname: Moreno
authors.forename: Ignacio
authors.initials: I
authors.lastname: Moriyón
authors.forename: Eynav
authors.initials: E
authors.lastname: Klechevsky
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Sangkon
authors.initials: S
authors.lastname: Oh
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D002002:Brucella / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005936:Glucans / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D005936:Glucans; D018950:Lipopolysaccharide Receptors; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C470409:TICAM1 protein, human; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse