Immuno-evasive tactics by schistosomes identify an effective allergy preventative.

Abstract

Many chronic inflammatory diseases can be improved by helminth infection, but the mechanisms are poorly understood. Allergy and helminthiasis are both associated with Th2-like immune responses; thus, defining how infection with parasites leads to reduced allergy has been particularly challenging. We sought to better understand this conundrum by evaluating host-parasite interactions involved in Th2 immunity in human schistosomiasis. Immune cells were cultured with schistosomes and the effect on CD23, an IgE receptor associated with resistance in schistosomiasis, was evaluated. Cells treated with schistosomes demonstrated reduced surface CD23 levels with a parallel accumulation of soluble (s) CD23 suggesting this IgE receptor is proteolytically cleaved by the parasite. Consistent with this hypothesis, a schistosome-generated (SG)-sCD23 fragment of 15 kDa was identified. SG-sCD23 inhibited IgE from binding to CD23 and FcεRI, but lacked the ability to bind CD21. These results suggested that schistosomes target IgE-mediated immunity in immuno-evasive tactics. Based on its characteristics, we predicted that SG-sCD23 would function as an efficacious allergy preventative. Treatment of human FcεRI-transgenic mice with recombinant (r) SG-sCD23 reduced the ability of human IgE to induce an acute allergic response in vivo. In addition, an optimized form of rSG-sCD23 with an introduced point mutation at Asp258 (D258E)to stabilize IgE binding had increased efficacy compared to native rSG-sCD23. Schistosome infection may thus inhibit allergic-like protective immune responses by increasing soluble IgE decoy receptors. Allergy treatments based on this naturally occurring phenomenon may be highly effective and have fewer side effects with long-term use.

• Authors: Qyana Griffith, YanMei Liang, Patrick Whitworth, Carlos Rodriguez-Russo, Ahmad Gul, Afzal A Siddiqui, John Connor, Pauline Mwinzi, Lisa Ganley-Leal
• Journal: Experimental parasitology (Exp Parasitol) Vol. 153 Pg. 139-50 (Jun 2015) ISSN: 1090-2449 [Electronic] United States
• PMID: 25819297 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, IgE
• Immunoglobulin E

Topics

• Adult
• Animals
• Host-Parasite Interactions
• Humans
• Hypersensitivity (immunology, prevention & control)
• Immune Evasion
• Immunoglobulin E (immunology)
• Male
• Mice
• Mice, Transgenic
• Receptors, IgE (administration & dosage, genetics, immunology)
• Schistosoma mansoni (genetics, immunology)
• Schistosomiasis mansoni (genetics, immunology, parasitology)
• Th2 Cells (immunology)
• Young Adult