Exposure to schistosome eggs protects mice from TNBS-induced colitis

Abstract

Crohn's disease results from dysregulated T helper (Th)1-type mucosal inflammation. Crohn's disease is rare in tropical countries but prevalent in developed countries with temperate climates, in which its incidence rose after 1940. In contrast, exposure to helminthic parasites is common in tropical countries but is rare in developed countries. Helminthic parasites induce immunomodulatory T cell responses in the host. We hypothesize that immunomodulatory responses due to helminths may attenuate excessive Th1-type inflammation. To test that hypothesis, mice were exposed to eggs of the helminth Schistosoma mansoni and then challenged rectally with trinitrobenzesulfonic acid (TNBS) to induce colitis. Schistosome egg exposure attenuated TNBS colitis and protected mice from lethal inflammation. Schistosome egg exposure diminished IFN-gamma and enhanced IL-4 production from alphaCD3-stimulated spleen and mesenteric lymph node cells of TNBS-treated mice. Schistosome egg exposure decreased colonic IFN-gamma but increased IL-10 mRNA expression in TNBS-treated mice. Intact signal transducer and activator of transcription 6 was required for attenuation of colitis. Exposure to helminths can decrease murine colonic inflammation.

Inhibition of type 1 diabetes in filaria‐infected non‐obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells

“…6 Experimentally, a number of helminth parasites, including the trematode Schistosoma mansoni and the nematodes Heligmosomoides polygyrus and Trichinella spiralis, prevent the onset or suppress the severity of type 1 diabetes in non-obese diabetic (NOD) mice, [12][13][14] experimental autoimmune encephalitis 15 and experimental colitis. [16][17][18] A clinical trial demonstrated that oral administration of porcine whipworm eggs improves symptoms in patients with inflammatory bowel disease. 19,20 To date, however, the exact mechanisms by which helminths protect against autoimmune diseases remain unknown.…”

“…Indeed, animal models of arthritis, 22 type I diabetes, [12][13][14]21,24 Graves hyperthyroidism, 25 experimental autoimmune encephalitis 15,26 and colitis [16][17][18] have all been inhibited or ameliorated by infections with helminth parasites or parasite-derived products. In this study, we found that infection with filarial helminths also protects against autoimmunity.…”

Schistosoma mansoni antigen-driven interleukin-10 production in infected asthmatic individuals

“…mansoni infection seems to be protective against asthma (Medeiros et al 2003, Araujo et al 2004. Using mice models of S. mansoni infection it has been demonstrated that this parasite also protects against the development of auto-immune disease such as diabetes, experimental auto-immune encephalopathy, and Crohn's disease (Cooke et al 1999, Elliott et al 2003, La Flamme et al 2003, Sewell et al 2003, Zaccone et al 2003. Some of these studies suggest that IL-10 is a key cytokine involved in the modulation of the inflammatory immune response observed in these diseases.…”

Macrophages – sensors and effectors coordinating skin damage and repair

“…Effect of helminth exposure Reference Preclinical model TNBS*-induced colitis in mice Protection from TNBS*-induced colitis [59] Pulmonary allergic inflammation in mice Protection from ovalbumin-induced airway hyperreactivity [60] Type 1 diabetes, non-obese diabetic mice Prevention of diabetes [61] Aged mice Attenuated alternative macrophage activation in aged vs. young mice upon helminth infection [62] Experimental autoimmune encephalitis (EAE)…”