Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the development of regulatory B cells

PLoS Pathogens

Louis Boon¹  Joke M. M. den Haan²  Henrike Veninga²  Cornelis H. Hokke³  Arifa Ozir-Fazalalikhan³  Mathilde A. M. Chayé³  Simone Haeberlein³  Luciën E. P. M. van der Vlugt³  Hermelijn H. Smits³  Astrid Voskamp³  Katja Obieglo³  Gabriele Schramm⁴  Lotte B. Westerhof⁵  Ruud H. P. Wilbers⁵  Arjen Schots⁵ 

[1] Bioceros, Utrecht, Netherlands;Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands;Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands;Experimental Pneumology, Priority Research Area Asthma & Allergy, Research Center Borstel, Parkallee, Borstel, Germany;Plant Science Department, Wageningen University and Research Centre, Droevendaalsesteeg, Wageningen, Netherlands

关键词: B cells;    Macrophages;    Schistosoma;    Schistosoma mansoni;    Flow cytometry;    Regulatory T cells;    Fluorescence microscopy;    Cytokines;   

DOI  :  10.1371/journal.ppat.1006539

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Infection with the helminth Schistosoma (S.) mansoni drives the development of interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest. However, both the involved antigen and cellular mechanisms that drive Breg cell development remain to be elucidated. Therefore, we investigated whether S. mansoni soluble egg antigens (SEA) directly interact with B cells to enhance their regulatory potential, or act indirectly on B cells via SEA-modulated macrophage subsets. Intraperitoneal injections of S. mansoni eggs or SEA significantly upregulated IL-10 and CD86 expression by marginal zone B cells. Both B cells as well as macrophages of the splenic marginal zone efficiently bound SEA in vivo, but macrophages were dispensable for Breg cell induction as shown by macrophage depletion with clodronate liposomes. SEA was internalized into acidic cell compartments of B cells and induced a 3-fold increase of IL-10, which was dependent on endosomal acidification and was further enhanced by CD40 ligation. IPSE/alpha-1, one of the major antigens in SEA, was also capable of inducing IL-10 in naïve B cells, which was reproduced by tobacco plant-derived recombinant IPSE. Other major schistosomal antigens, omega-1 and kappa-5, had no effect. SEA depleted of IPSE/alpha-1 was still able to induce Breg cells indicating that SEA contains more Breg cell-inducing components. Importantly, SEA- and IPSE-induced Breg cells triggered regulatory T cell development in vitro. SEA and recombinant IPSE/alpha-1 also induced IL-10 production in human CD1d+ B cells. In conclusion, the mechanism of S. mansoni-induced Breg cell development involves a direct targeting of B cells by SEA components such as the secretory glycoprotein IPSE/alpha-1.

【 授权许可】

CC BY