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

• Published in: PLoS pathogens Vol. 13; no. 7; p. e1006539
• Main Authors: Haeberlein, Simone, Obieglo, Katja, Ozir-Fazalalikhan, Arifa, Chayé, Mathilde A M, Veninga, Henrike, van der Vlugt, Luciën E P M, Voskamp, Astrid, Boon, Louis, den Haan, Joke M M, Westerhof, Lotte B, Wilbers, Ruud H P, Schots, Arjen, Schramm, Gabriele, Hokke, Cornelis H, Smits, Hermelijn H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2017; Public Library of Science (PLoS)
• Subjects: Acidification; Animals; Antigens; Antigens, Helminth - genetics; Antigens, Helminth - immunology; B cells; B-Lymphocytes, Regulatory - immunology; Biology and Life Sciences; Bisphosphonates; CD1d antigen; CD40 antigen; CD86 antigen; Clodronic acid; Compartments; Cytokines; Dendritic cells; Depletion; Egg Proteins - genetics; Egg Proteins - immunology; Eggs; Female; Fluke infections; Flukes; Funding; Glycoproteins; Grants; Helminth Proteins - genetics; Helminth Proteins - immunology; Humans; Immunology; In vitro methods and tests; Infections; Inflammatory diseases; Interleukin 10; Interleukin-10 - immunology; Liposomes; Lymphocytes B; Lymphocytes T; Macrophages; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Ovum - immunology; Parasitology; Physiological aspects; Plant sciences; Plants; Research and Analysis Methods; Respiratory tract; Respiratory tract diseases; Schistosoma mansoni - genetics; Schistosoma mansoni - immunology; Schistosomiasis mansoni - genetics; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - parasitology; Spleen; Tobacco
• ISSN: 1553-7366; 1553-7374; 1553-7374
• DOI: 10.1371/journal.ppat.1006539

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.