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

PLoS Pathogens

Patrick Lecine¹  Melissa Dullaers¹  Marielle Mello¹  Romain Banchereau²  Edgardo Moreno²  Jacques Banchereau²  Yves Levy²  Anna Martirosyan³  Alexandre Muller³  Gerard Zurawski³  SangKon Oh³  Ignacio Moriyón³  Hélène Dutartre⁴  Lee Leserman⁵  Eynav Klechevsky⁵  Camino Pérez-Gutierrez⁵  Sandy Zurawski⁵  Jean-Pierre Gorvel⁵  Suzana Pinto Salcedo⁶ 

[1] Baylor Institute for Immunology Research and INSERM U899, Dallas, Texas, United States of America;Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France;Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille, France;Fundación Investigación Sanitaria Illes Balears-CSIC, Bunyola, Spain;Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France;Laboratory of Immunoregulation and Mucosal Immunity, Department of Pneumology, Gent, Belgium

关键词: T cells;    Cytotoxic T cells;    Brucella;    Immunologic adjuvants;    Glucans;    Antigens;    Flow cytometry;    Vaccines;   

DOI  :  10.1371/journal.ppat.1002983

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY