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

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.

Th2 signals are not essential for the anti‐arthritic effects of Trichinella spiralis in mice

“…Trichinella sp infection or their products protect experimental hosts from several immune diseases 25 such as type 1 diabetes (T1D) in NOD mice, 26 inflammatory bowel diseases (IBD), [27][28][29][30][31][32][33][34] experimental autoimmune encephalomyelitis (EAE) 35,36 and adjuvant arthritis. 37 Regarding other helminths, Th2 signals were reported to be essential for the anti-arthritic effects. [6][7][8] Recently, Cheng et al 38 reported…”

The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

“…Furthermore, current studies suggest that early infection of certain parasites may prevent the development of autoimmune diseases, including allergic disease and RA [7], and the mechanisms are associated with immune responses mediated by parasite infection. For example, it has been shown that Schistosoma japonicum infection and Trichinella spiralis derived antigen could reduce the severity of collageninduced arthritis [8], via immune reactions related to IL-4 and Treg Cells mediated by parasite antigens in CIA mice.…”

Clonorchis Sinensis-Derived Protein Attenuates Inflammation and New Bone Formation in Ankylosing Spondylitis

“…Regarding on the helminths therapy targeting arthritis, experimental infections with S. japonicum, S. mansoni, Ascaris suum and Hymenolepsis diminuta, or administrations of their proteins have been shown to possess inhibitory effects on murine collagen-induced arthritis [17][18][19][20][21]. In thses studies, antiarthritic activity is mediated by up-regulation of the Foxp3 + Tregs with subsequent favorable modulation of both pro-and anti-in ammatory cytokines [20]. We speculated that C. sinensis, a liver uke found predominantly in Asia including Korea and China, could be an alternative candidate of Schistosoma.…”

“…First, we could not clarify the exact mechanism in the inhibition of Th17 response. However, this might be mediated by upregulation of regulatory cell populations such as CD4 + CD25 + Foxp3 + T cells or IL-10 secreting macrophages [20,26,27]. The inverse correlation of IL-10 with Th17 cells has been addressed both in humans and an experimental murine model [17,33].…”