Brucella β 1,2 Cyclic Glucan Is an Activator of Human and Mouse Dendritic Cells

Anna Martirosyan, Camino Pérez-Gutierrez, Romain Banchereau, Hélène Dutartre, Patrick Lecine, Melissa Dullaers, Marielle Mello, Suzana Pinto Salcedo, Alexandre Muller, Lee Leserman, Yves Levy, Gerard Zurawski, Sandy Zurawski, Edgardo Moreno, Ignacio Moriyón, Eynav Klechevsky, Jacques Banchereau, Sang Kon Oh, Jean Pierre Gorvel

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Article numbere1002983
JournalPLoS pathogens
Volume8
Issue number11
DOIs
StatePublished - Nov 2012

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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