1. Brucella β 1,2 cyclic glucan is an activator of human and mouse dendritic cells.
- Author
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Martirosyan A, Pérez-Gutierrez C, Banchereau R, Dutartre H, Lecine P, Dullaers M, Mello M, Salcedo SP, Muller A, Leserman L, Levy Y, Zurawski G, Zurawski S, Moreno E, Moriyón I, Klechevsky E, Banchereau J, Oh S, and Gorvel JP
- Subjects
- Adaptor Proteins, Vesicular Transport genetics, Adaptor Proteins, Vesicular Transport immunology, Animals, Brucella chemistry, Cells, Cultured, Glucans chemistry, Glucans pharmacology, Humans, Lipopolysaccharide Receptors genetics, Lipopolysaccharide Receptors immunology, Mice, Mice, Knockout, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 immunology, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 immunology, Adjuvants, Immunologic, Brucella immunology, CD4-Positive T-Lymphocytes immunology, Dendritic Cells immunology, Glucans immunology
- 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.
- Published
- 2012
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