Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

PLoS Pathogens

Richard Speare¹  Luciana M. Oliveira²  Jeffrey M. Bethony²  James Daveson³  Di Jones³  James S. McCarthy⁴  Christian R. Engwerda⁴  Henry J. McSorley⁵  Soraya Gaze⁵  Alex Loukas⁵  John Croese⁶ 

[1] Anton Breinl Centre, James Cook University, Townsville, Queensland, Australia;George Washington University, Washington D.C., United States of America;Princess Alexandra Hospital, Brisbane, Queensland, Australia;Queensland Institute of Medical Research, Brisbane, Queensland, Australia;Queensland Tropical Health Alliance and School of Public Health and Tropical Medicine, James Cook University, Cairns, Queensland, Australia;The Townsville Hospital and James Cook University, Townsville, Queensland, Australia

关键词: Hookworms;    Helminth infections;    Cytokines;    Biopsy;    Immune response;    Parasitic diseases;    Gluten;    Necator americanus;   

DOI  :  10.1371/journal.ppat.1002520

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY