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

نویسندگان

  • 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
  • SangKon Oh
  • Jean-Pierre Gorvel
چکیده

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.

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عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2012