Suppression of Inflammatory Immune Responses in Celiac Disease by Experimental Hookworm Infection

McSorley, HJ; Gaze, S; Daveson, J; Jones, D; Anderson, RP; Clouston, A; Ruyssers, NE; Speare, R; McCarthy, JS; Engwerda, CR; Croese, J; Loukas, A

Author(s): McSorley, HJ; Gaze, S; Daveson, J; Jones, D; Anderson, RP; Clouston, A; Ruyssers, NE; Speare, R; McCarthy, JS; Engwerda, CR; Croese, J; Loukas, A;
Details: Publication Year 2011-09-16,Volume 6,Issue #9,Page e24092
Journal Title: PLOS ONE
Publication Type: Journal Article
Abstract: We present immunological data from two clinical trials where the effect of experimental human hookworm (Necator americanus) infection on the pathology of celiac disease was evaluated. We found that basal production of Interferon-(IFN-)gamma and Interleukin- (IL-)17A from duodenal biopsy culture was suppressed in hookworm-infected participants compared to uninfected controls. Increased levels of CD4+CD25+Foxp3+cells in the circulation and mucosa are associated with active celiac disease. We show that this accumulation also occurs during a short-term (1 week) oral gluten challenge, and that hookworm infection suppressed the increase of circulating CD4+CD25+Foxp3+cells during this challenge period. When duodenal biopsies from hookworm-infected participants were restimulated with the immunodominant gliadin peptide QE65, robust production of IL-2, IFN-gamma and IL-17A was detected, even prior to gluten challenge while participants were strictly adhering to a gluten-free diet. Intriguingly, IL-5 was produced only after hookworm infection in response to QE65. Thus we hypothesise that hookworm-induced TH2 and IL-10 cross-regulation of the TH1/TH17 inflammatory response may be responsible for the suppression of these responses during experimental hookworm infection.
Publisher: PUBLIC LIBRARY SCIENCE
Keywords: celiac disease ; inflammatory response ; hookworm infection ; duodenal biopsy culture
Research Division(s): Immunology
Publisher's Version: https://doi.org/10.1371/journal.pone.0024092
Open Access at Publisher's Site: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174943/
Terms of Use/Rights Notice: Copyright: © 2011 McSorley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Documents: journal.pone.0024092.pdf - (0.78MB, application/pdf)

Creation Date: 2011-09-16 12:00:00