Heligmosomoides polygyrus inhibits established colitis in IL‐10‐deficient mice

Abstract

Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less‐developed countries. Helminths, common in less‐developed countries, may induce immunoregulatory circuits protective against IBD. IL‐10–/– mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL‐10–/– mice released IFN‐γ and IL‐12. The ongoing piroxicam‐induced colitis could be partially blocked with anti‐IL‐12 monoclonal antibody suggesting that the inflammation was at least partly IL‐12 dependent. Colonization of piroxicam‐treated colitic IL‐10–/– mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL‐12 and IFN‐γ production. H. polygyrus augmented mucosal IL‐13, but not IL‐4 or IL‐5 production. Transfer of mesenteric lymph node (MLN) T cells from IL‐10–/– animals harboring H. polygyrus into colitic IL‐10–/– recipients inhibited colitis. MLN T cells from worm‐free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL‐10–/– colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL‐13 production and can be adoptively transferred by MLN T cells.

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.…”

Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3+ cells

“…However, such effects can be beneficial by downregulating inflammatory reactions to allergens and inflammatory disorders of the intestinal tract. Studies in animal models showed that helminths can suppress airway hyperreactivity and colitis [6][7][8] and nematodes have been used to efficiently treat human inflammatory bowel disease in clinical trials [9,10]. …”

“…It has been demonstrated that nematode infections may prevent and control undesired immune reactions [6][7][8][9][10][11][12]30]. Several studies showed that the beneficial effects of the infections could be mimicked by transfer of Treg derived from nematode-infected donors to naïve recipients rendering them refractory to the inflammatory disorders such as asthma and colitis [6,8,11,12]. These data indicate that circuits of Treg action during nematode infection may also modulate unrelated bystander immune reactions and supports the view of Treg as important immunoregulators that can be modulated by parasites.…”

Usage of Parasites as Alternative Therapy

“…Özellikle IL10 eksikliği görülen farelerde kolaylıkla kronik kolit gelişebileceği gözlenmiştir. Bu tür farelere dışa-rıdan verilen Trichuris muris veya Heligmosomoides polygyrus gibi helmentlerin ise kolitin gelişimini inhibe ederken IL10 düzeyini de tersine çevirdiği gözlenmiştir (7) . Ayrıca dışarıdan H.polygyrus verilen farelerde kolite karşı daha resistan bir barsak yapısına ulaşıldığı da göste-rilmiştir.…”