BACKGROUND: Several lines of evidence have shown that helminthiasis can significantly reduce disease severity in animal models of intestinal inflammation, airway inflammation/hyperreactivity, diabetes, and multiple sclerosis. Identification and characterization of helminth-derived immunomodulatory molecules that contribute to anticolitis effects could lead to new therapeutic approaches in inflammatory bowel diseases (IBDs) without the need for helminth infection. We evaluated the therapeutic potential of adult human hookworm, Ancylostoma ceylanicum, crude (Aw) and excreted/secreted (ES) products on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice. METHODS: Colitis was induced by 5% DSS oral administration for 7 days. Clinical disease severity was monitored daily during concomitant intraperitoneal treatment with helminth-derived products. Additionally, several pathways of immunological modulation induced by A. ceylanicum products (MPO, EPO, Th1, Th2, and Th17 cytokine responses) in the inflamed intestinal microenvironment were assessed. Finally, the histopathological profile of the colon was characterized. RESULTS: Hookworm products are able to modulate the potent proinflammatory response induced by DSS, mainly through the downregulation of Th1 and Th17 cytokines. These proteins also reduce clinical and colonic microscopic inflammation scores as well as EPO and MPO activity. CONCLUSIONS: Ancylostoma ceylanicum Aw and ES mediators have an important therapeutic potential in experimental colitis in mice, which may provide a more socially acceptable form of therapy for patients with IBDs as opposed to using living worms. Our results support the urgency of further isolation and recombinant expression of active hookworm products responsible for the beneficial effects on colitis.
BACKGROUND: Several lines of evidence have shown that helminthiasis can significantly reduce disease severity in animal models of intestinal inflammation, airway inflammation/hyperreactivity, diabetes, and multiple sclerosis. Identification and characterization of helminth-derived immunomodulatory molecules that contribute to anticolitis effects could lead to new therapeutic approaches in inflammatory bowel diseases (IBDs) without the need for helminth infection. We evaluated the therapeutic potential of adult human hookworm, Ancylostoma ceylanicum, crude (Aw) and excreted/secreted (ES) products on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice. METHODS:Colitis was induced by 5% DSS oral administration for 7 days. Clinical disease severity was monitored daily during concomitant intraperitoneal treatment with helminth-derived products. Additionally, several pathways of immunological modulation induced by A. ceylanicum products (MPO, EPO, Th1, Th2, and Th17 cytokine responses) in the inflamed intestinal microenvironment were assessed. Finally, the histopathological profile of the colon was characterized. RESULTS: Hookworm products are able to modulate the potent proinflammatory response induced by DSS, mainly through the downregulation of Th1 and Th17 cytokines. These proteins also reduce clinical and colonic microscopic inflammation scores as well as EPO and MPO activity. CONCLUSIONS:Ancylostoma ceylanicum Aw and ES mediators have an important therapeutic potential in experimental colitis in mice, which may provide a more socially acceptable form of therapy for patients with IBDs as opposed to using living worms. Our results support the urgency of further isolation and recombinant expression of active hookworm products responsible for the beneficial effects on colitis.
Authors: Phurpa Wangchuk; Catherine Shepherd; Constantin Constantinoiu; Rachael Y M Ryan; Konstantinos A Kouremenos; Luke Becker; Linda Jones; Geraldine Buitrago; Paul Giacomin; David Wilson; Norelle Daly; Malcolm J McConville; John J Miles; Alex Loukas Journal: Infect Immun Date: 2019-03-25 Impact factor: 3.441
Authors: Pedro H Gazzinelli-Guimaraes; Rafael de Queiroz Prado; Alessandra Ricciardi; Sandra Bonne-Année; Joshua Sciurba; Erik P Karmele; Ricardo T Fujiwara; Thomas B Nutman Journal: J Clin Invest Date: 2019-08-05 Impact factor: 14.808