Cystatin from Filarial Parasites Suppress the Clinical Symptoms and Pathology of Experimentally Induced Colitis in Mice by Inducing T-Regulatory Cells, B1-Cells, and Alternatively Activated Macrophages.

Nalini Bisht,Vishal Khatri,Ramaswamy Kalyanasundaram,Nikhil Chauhan

doi:10.3390/biomedicines7040085

Abstract

Potential alternative therapeutic strategies for immune-mediated disorders are being increasingly recognized and are studied extensively. We previously reported the therapeutic potential of Brugia malayi derived recombinant cystatin (rBmaCys) in attenuating clinical symptoms of experimental colitis. The aim of this study was to elucidate the mechanisms involved in the rBmaCys-induced suppression of inflammation in the colon. Our results show that, the frequency of CD4+CD25+FoxP3+ regulatory T-cells was elevated in the colon and mesenteric lymph nodes. Similarly, the peritoneal macrophages recovered from the rBmaCys-treated colitis mice were alternatively activated and displayed reduced expression of TNF-α and IL-6. Another finding was significant increases in IgM+B1a-cells in the peritoneal cavity of mice following rBmaCys-treatment. These findings suggested that the regulatory cell network promoted by the rBmaCys in the colon and associated lymphoid tissues is important for its anti-inflammatory activity in the dextran sulfate sodium (DSS)-induced colitis mice.

Highlights

Helminth therapy has emerged as an efficient alternative to traditional treatments against autoimmune and inflammatory disorders
These results suggest that Tregulatory Cells (Tregs) are potentially among one of the cells that contributed in the colon tissue of recombinant B. malayi Cystatin (rBmaCys)-treated mice
Results presented inBertelsen, this study show that treatment withpårBmaCys significantly reduced the clinical

Summary

Introduction

Helminth therapy has emerged as an efficient alternative to traditional treatments against autoimmune and inflammatory disorders. Th1 to Th2 biased responses, infection with helminth parasites can suppress or prevent symptoms of autoimmune and inflammatory diseases [1,2]. Cystatins play a pivotal role in (i) suppressing pathogenicity in immune-mediatory disorders, (ii) modulating antigen processing and presentation by antigen presenting cells, (iii) inducing T-cell mediated immunosuppression, and (iv) inhibiting release of proinflammatory cytokines. Several pathogenic organisms including parasites are known to produce cystatins with defined immunomodulatory roles in the host [4]. These parasite-derived cystatins are well-known for their ability to trigger immunosuppressive cytokines from a number of immune cells [6]. Given its potent immunoregulatory role, cystatin of helminth parasites such as Ascaris lumbricoides [7], Schistosoma japonicum, Acanthocheilonema viteae, Clonorchis

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