Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection
McSorley, Henry, Gaze, Soraya, Davidson, James, Jones, Dianne, Anderson, Robert P., Coulston, Andrew, Ruyssers, Nathalie, Speare, Richard, McCarthy, James, 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). pp. 1-7.
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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.
|Item Type:||Article (Refereed Research - C1)|
Licensed under a Creative Commons License (CC BY 2.5)
|Funders:||Broad Foundation, National Health and Medical Research Council|
|Date Deposited:||05 Dec 2011 06:22|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%|
|Citation Count from Web of Science||
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