Abstract
BackgroundMany evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases.Methods and FindingsColitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES) intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN), and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells) and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17) in the spleens, MLN and colon of treated mice.ConclusionsOur results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.
Highlights
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammatory conditions of the gastrointestinal tract
Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice
We further explored the therapeutic effects of ES products from T. spiralis adult worms (AES) on dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice
Summary
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammatory conditions of the gastrointestinal tract. A significant number of experimental studies have provided support for this hypothesis and demonstrated that certain helminths, including Trichinella spiralis, have immunomodulatory effects on parasite-induced inflammation and on other immunopathologies, such as allergies and autoimmune diseases [8,9,10,11,12,13]. The possible mechanism that underlies the hygiene hypothesis is the immunomodulatory effects of the molecules secreted by parasitic helminthes during parasitism on the host immune response as a strategy to evade host immune attack. These immunomodulations include a strong Th2 immune response and/or regulatory cytokines (IL-10, TGF-b) and Tregulatory (Treg) response to down-regulate the cellular responses to the parasites. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases
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