title: Characterising the mucosal and systemic immune responses to experimental human hookworm infection.
abstract: 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.
authors.affiliation: Queensland Tropical Health Alliance and School of Public Health and Tropical Medicine, James Cook University, Cairns, Queensland, Australia.
authors.forename: Soraya
authors.initials: S
authors.lastname: Gaze
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McSorley
authors.forename: James
authors.initials: J
authors.lastname: Daveson
authors.forename: Di
authors.initials: D
authors.lastname: Jones
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bethony
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Oliveira
authors.forename: Richard
authors.initials: R
authors.lastname: Speare
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.forename: Christian R
authors.initials: CR
authors.lastname: Engwerda
authors.forename: John
authors.initials: J
authors.lastname: Croese
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000723:Ancylostomatoidea / Q000276:immunology*; D000818:Animals; D000947:Antigens, Helminth / Q000097:blood / Q000276:immunology; D001315:Australia; D015551:Autoimmunity / Q000276:immunology; D055050:Diet, Gluten-Free; D006725:Hookworm Infections / Q000276:immunology* / Q000469:parasitology; D006805:Human Experimentation; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007378:Interleukins / Q000097:blood* / Q000378:metabolism; D007814:Larva; D009092:Mucous Membrane / Q000378:metabolism; D010270:Parasite Egg Count; D050697:Retinal Dehydrogenase / Q000097:blood / Q000378:metabolism; D016037:Single-Blind Method; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D007378:Interleukins; D016212:Transforming Growth Factor beta; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase