Ligation of Dectin-2 with a novel microbial ligand promotes adjuvant activity for vaccination

PLoS Pathogens

Marcel Wüthrich¹  Robert Zarnowski²  Huafeng Wang³  Taek-Jin Lee³  Scott J. Fites³  Bruce Klein³  Kevin Galles³  Richard Merkhofer³  Tristan Brandhorst³ 

[1] Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States of America;Department of Medicine (Infectious Disease Division), University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States of America;Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States of America

关键词: T cells;    Vaccines;    Cytokines;    Immunologic adjuvants;    Yeast;    Fungi;    C;    ida albicans;    Alumni;   

DOI  :  10.1371/journal.ppat.1006568

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The development of vaccines against fungi and other intracellular microbes is impeded in part by a lack of suitable adjuvants. While most current vaccines against infectious diseases preferentially induce production of antibodies, cellular immunity is essential for the resolution of fungal infections. Microbes such as fungi and Mycobacterium tuberculosis require Th17 and Th1 cells for resistance, and engage the C-type lectin receptors including Dectin-2. Herein, we discovered a novel Dectin-2 ligand, the glycoprotein Blastomyces Eng2 (Bl-Eng2). Bl-Eng2 triggers robust signaling in Dectin-2 reporter cells and induces IL-6 in human PBMC and BMDC from wild type but not Dectin-2-/- and Card9-/- mice. The addition of Bl-Eng2 to a pan-fungal subunit vaccine primed large numbers of Ag-specific Th17 and Th1 cells, augmented activation and killing of fungi by myeloid effector cells, and protected mice from lethal fungal challenge, revealing Bl-Eng2’s potency as a vaccine adjuvant. Thus, ligation of Dectin-2 by Bl-Eng-2 could be harnessed as a novel adjuvant strategy to protect against infectious diseases requiring cellular immunity.

【 授权许可】

CC BY