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article · PLoS ONE

Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens in Adjuvant Arthritis in Rats: Role of FOXP3+ Treg Cells

201672 citationsOpen accessKafr el-Sheikh University

In plain language

This study evaluated the protective effects of autoclaved antigens derived from the parasites Schistosoma mansoni and Trichinella spiralis against rheumatoid arthritis in a rat model. Arthritis was induced using complete Freund's adjuvant, and animals received two intradermal doses of either parasite antigen over a four-week monitoring period. Both treatments slowed the progression of polyarthritis symptoms, improved gait, aided body weight gain, and restricted joint inflammation to the subcutaneous tissue. Treatment decreased elevated serum IL-17, increased levels of IFN-gamma and IL-10, and significantly raised numbers of Foxp3+ regulatory T cells, with the Schistosoma mansoni antigen demonstrating stronger overall protective effects. Using heat-inactivated parasite antigens avoids the complications linked to live parasitic infection, offering a potential foundation for developing new immunotherapies to manage rheumatoid arthritis.

Key takeaways

  • Treatment with autoclaved Schistosoma mansoni and Trichinella spiralis antigens attenuated the progression of adjuvant arthritis in rats.
  • Antigen administration improved animal gait, supported body weight gain, and restricted paw inflammation.
  • The antigens altered immune responses by reducing serum IL-17, increasing IFN-gamma and IL-10, and expanding Foxp3+ regulatory T cells.
  • The Schistosoma mansoni antigen demonstrated greater protective efficacy than the Trichinella spiralis antigen.
  • Using autoclaved parasitic antigens bypasses the health risks associated with administering live parasitic infections.

Why it matters

Rheumatoid arthritis is a debilitating autoimmune condition that requires effective therapies to control inflammation. Helminth-derived treatments show promise for treating autoimmune diseases, but using live worms poses health risks. Demonstrating that heat-inactivated, non-living parasitic antigens can calm immune responses and reduce joint damage in animals offers a safer principle for designing future arthritis treatments.

Commercialisation angle

This research could inform the development of biological therapeutics for autoimmune disorders such as rheumatoid arthritis, targeting pharmaceutical and biotherapeutic developers. However, the work represents early-stage preclinical research conducted solely in a rodent model. Significant translational development, including safety profiling, formulation optimisation, and human clinical trials, remains necessary before any commercial therapeutic application can be realised.

AI-generated from the published abstract. Always read the original work before citing.

Abstract

A growing body of evidence supports the concept of helminths therapy in a variety of autoimmune diseases. Here, we aimed to investigate the protective effects of autoclaved Schistosoma mansoni antigen (ASMA) and Trichinella spiralis antigen (ATSA) on the clinical and immunopathological features of rheumatoid arthritis (RA). Adjuvant arthritis was induced by subcutaneous and intradermal injections of complete Freund's adjuvant into the plantar surface of the right hind paw and the root of the tail, respectively. Rats were randomly assigned to serve as normal control, untreated arthritis, ASMA or ATSA-treated arthritis groups. Antigens were given by intradermal injection in two doses, two weeks apart. The development, progression of arthritic features, and the impact on animals' gait and body weight were followed up for 4 weeks. The associated changes in serum cytokines (IL-17, IFN-γ and IL-10), joints' histopathology and immunohistochemistry of Foxp3+ T regulatory cells (Tregs) were evaluated at the end of the study. Treatment with either ASMA or ATSA attenuated the progression of clinical features of polyarthritis, improved gait and body weight gain, reduced the elevated serum IL-17 and further increased both IFN-γ and IL-10. Histopathologically, this was associated with a remarkable regression of paws' inflammation that was limited only to the subcutaneous tissue, and a significant increase in the number of Foxp 3+ cells versus the untreated arthritis group. In conclusion, both Schistosoma mansoni and Trichinella spiralis derived antigens exerted protective effect against adjuvant arthritis with better effect achieved by ASMA treatment. This anti-arthritic activity is attributed to upregulation of the Foxp3+ Tregs, with subsequent favorable modulation of both pro- and anti-inflammatory cytokines. The use of autoclaved parasitic antigens excludes the deleterious effects of imposing helminthic infection by using live parasites, which may pave the way to a new therapeutic modality in treating RA.

Research topics

  • Parasites and Host Interactions
  • Research on Leishmaniasis Studies
  • Parasite Biology and Host Interactions

Sustainable Development Goals

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DOI: 10.1371/journal.pone.0165916

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