Excretory/Secretory Products from Trichinella spiralis Adult Worms Ameliorate DSS-Induced Colitis in Mice

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.

Trichinella spiralis paramyosin activates mouse bone marrow-derived dendritic cells and induces regulatory T cells

“…Even though r Ts Pmy only induced bone marrow-derived DCs to a semi-mature status, it did not affect their abilities to induce Treg cells, confirming that semi-mature DCs also induce tolerance [39, 40]. Our results are consistent with other investigations that showed T. spiralis excretory-secretory antigen-stimulated dendritic cells alleviated experimental autoimmune encephalomyelitis or DSS-induced colitis through inducing Treg that increased the secretion of IL-4, IL-10 and TGF-β [4, 41, 42]. However, r Ts Pmy immunization only induced CD4 + CD25 − Foxp3 + T cells, not CD4 + CD25 + Foxp3 + T cells, in immunized mice.…”

“…The newborn larvae are released from sexually-mature adult worms and soon migrate to skeletal muscles to form encysted muscle larvae that may live for several years and cause a chronic infection [3]. How the Trichinella parasite maintains the chronic infection within the host without being recognized and attacked by the host’s immune system remains unknown [4]. Understanding the mechanism underlying the immune evasion would greatly benefit the design of preventive/therapeutic vaccines or drugs to control the infection.…”

Treatment with Cestode Parasite Antigens Results in Recruitment of CCR2 + Myeloid Cells, the Adoptive Transfer of Which Ameliorates Colitis

“…Many studies show that tissue extracts or E/S products from helminths can suppress mammalian immune cell activation in vitro (29)(30)(31)(32) and ameliorate the severity of inflammatory disease in murine model systems (14,18,19,29,30,33,34). The demonstration herein that systemic administration of a crude extract of adult H. diminuta parasites dosedependently inhibits DSS-induced colitis adds to awareness of the ability of helminth-derived molecules to suppress intestinal inflammation (19,21,35).…”

“…Similarly, and as an alternative to viable infection, systemic administration of helminth-derived antigens can ameliorate colitis in animal models. As examples, the excretory/secretory (E/S) products from adult T. spiralis reduced DSS-induced colitis (18) and S. mansoni egg antigens ameliorated immunemediated colitis (19): in both instances, suppression of TH1 and TH17 cytokines correlated with the beneficial anticolitic effect. While encouraging, the precise mechanism of action of any helminth-derived extract or molecule to block colitis or other inflammatory diseases is not well understood.…”

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

“…spiralis in autoimmune and allergic diseases using either crude muscle larval antigens, excretory products or infection [7, 39] its role in RA has not been addressed. To the best of our knowledge, this is also the first study demonstrating the ameliorative effect of ASMA on the clinical signs and structural derangements in AA.…”