Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection

McSorley, Henry J., Gaze, Soraya, Daveson, James, Jones, Dianne, Anderson, Robert P., Clouston, Andrew, Ruyssers, Nathalie E., Speare, Richard, McCarthy, James S., Engwerda, Christian R., Croese, John and Loukas, Alex (2011) Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. PLoS One, 6 9: e24092-1-e24092-7. doi:10.1371/journal.pone.0024092

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Author McSorley, Henry J.
Gaze, Soraya
Daveson, James
Jones, Dianne
Anderson, Robert P.
Clouston, Andrew
Ruyssers, Nathalie E.
Speare, Richard
McCarthy, James S.
Engwerda, Christian R.
Croese, John
Loukas, Alex
Title Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-09
Sub-type Article (original research)
DOI 10.1371/journal.pone.0024092
Open Access Status DOI
Volume 6
Issue 9
Start page e24092-1
End page e24092-7
Total pages 7
Place of publication San Francisco, CA, U.S.A.
Publisher Public Library of Science
Collection year 2012
Language eng
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-)γ 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-γ 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.
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Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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Created: Tue, 04 Oct 2011, 11:16:02 EST by Matthew Lamb on behalf of School of Medicine