Co-infection with helminths is also known to attenuate murine models of autoimmunity and inflammatory bowel disease. Despite being classed as pathogens, helminth parasites are being proposed as treatments for allergic and autoimmune diseases. Preliminary observations suggest that intentional infection with the zoophilic Trichuris suis is safe, and reduces the activity of inflammatory bowel disease. However, dosing with T. suis every three weeks is required to maintain ongoing infection because the human host does not sustain development of T. suis to maturity. Necator americanus is a long-lived hematophagous, humanspecific gastrointestinal nematode that infects over 500 million people in developing countries where heavy infection causes iron deficiency anemia, and is associated with reduced physical and intellectual development. Experimental infection of healthy volunteers with NA infective third-stage larvae may cause an acute, painful enteropathy. Recent published data indicate that low-dose inocula of NA are better tolerated, and because they do not proliferate in humans, a defined dose can be administered and later fully eliminated with anthelmintic therapy. A further advantage is infected individuals pose no risk to others because hookworms are soil-transmitted and cannot be propagated in modern sanitary environments. We chose NA and celiac disease to explore the relationship between helminth infection and intestinal inflammation due to a well 2-O-galloylhyperin characterised dietary antigen, gluten. Our previous studies with this hookworm have provided us with a pure source of infective larvae. Individuals carrying chronic infection with hookworms in endemic settings demonstrate parasite-specific TH2 responses, but TH1 and TH2 immune responses to other antigens are diminished. Celiac disease is uniquely suited to explore the effects of helminth infection; it is common and remission is achieved with elimination of dietary gluten allowing host-parasite interaction to be studied free of potential artefacts caused by medications. Clinical studies in volunteers with CD also have the advantage that the effects of deliberate gluten exposure can be measured by symptom response,LOUREIRIN-B in blood and intestinal tissue. Over 90% of people with CD possess genes encoding the major histocompatability Class II molecule, HLA-DQ2, and HLA DQ2-restricted CD4 + T cells specific for deamidated gluten peptides can be isolated from intestinal tissue. HLA DQ2restricted CD4 + TH1 cells specific for deamidated gluten including the immunodominant a-gliadin 17-mer p57-73 peptide are also present in blood after oral wheat challenge. In this study, we undertook a clinical trial to test whether NA infection reduces the immunotoxic effects of gluten in CD. All vials and pipettes were examined following inoculation to ensure that there were no residual hookworm larvae. We propose that chronic helminthiasis, such as hookworm infection, may be immunomodulatory and alter pathogenic immune responses in vivo. In this Phase 1b/2a trial, we have established an experimental model allowing us to explore how hookworm infection alters the effects of gluten in CD. Chronic hookworm infection can be reliably and safely established in subjects with well controlled disease. Lacking precedent, the size of this demanding study was small. We observed at best weak trends towards reduced numbers of gluten peptide-specific T cells in blood and histological damage following wheat challenge in CD. As has been reported in another trial, standard fecal microscopy is relatively insensitive in light infection; a negative test does not exclude colonization. All patients inoculated acquired adult hookworms in the intestine.