Background and AimsThe association between hygiene and prevalence of autoimmune disease has been
attributed in part to enteric helminth infection. A pilot study of
experimental infection with the hookworm Necator americanus
was undertaken among a group of otherwise healthy people with celiac disease
to test the potential of the helminth to suppress the immunopathology
induced by gluten.MethodsIn a 21-week, double-blinded, placebo-controlled study, we explored the
effects of N. americanus infection in 20 healthy,
helminth-naïve adults with celiac disease well controlled by diet.
Staged cutaneous inoculations with 10 and 5 infective 3rd stage
hookworm larvae or placebo were performed at week-0 and -12 respectively. At
week-20, a five day oral wheat challenge equivalent to 16 grams of gluten
per day was undertaken. Primary outcomes included duodenal Marsh score and
quantification of the immunodominant α-gliadin peptide (QE65)-specific
systemic interferon-γ-producing cells by ELISpot pre- and post-wheat
challenge.ResultsEnteric colonisation with hookworm established in all 10 cases, resulting in
transiently painful enteritis in 5. Chronic infection was asymptomatic, with
no effect on hemoglobin levels. Although some duodenal eosinophilia was
apparent, hookworm-infected mucosa retained a healthy appearance. In both
groups, wheat challenge caused deterioration in both primary and several
secondary outcomes.ConclusionsExperimental N. americanus infection proved to be safe and
enabled testing its effect on a range of measures of the human autoimmune
response. Infection imposed no obvious benefit on pathology.Trial RegistrationClinicalTrials.gov NCT00671138
Food bolus obstruction can be safely managed by the push technique. EE is an important cause of food bolus obstruction that can be suspected on history and endoscopic appearance and confirmed on histology.
The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.
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