1. Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection.
- Author
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McSorley HJ, Gaze S, Daveson J, Jones D, Anderson RP, Clouston A, Ruyssers NE, Speare R, McCarthy JS, Engwerda CR, Croese J, and Loukas A
- Subjects
- Animals, Biopsy, CD4 Antigens immunology, CD4 Antigens metabolism, Celiac Disease parasitology, Celiac Disease pathology, Cells, Cultured, Clinical Trials as Topic, Duodenum metabolism, Duodenum pathology, Forkhead Transcription Factors immunology, Forkhead Transcription Factors metabolism, Gliadin immunology, Host-Parasite Interactions immunology, Humans, Immunohistochemistry, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-17 immunology, Interleukin-17 metabolism, Interleukin-2 immunology, Interleukin-2 metabolism, Interleukin-2 Receptor alpha Subunit immunology, Interleukin-2 Receptor alpha Subunit metabolism, Interleukin-5 immunology, Interleukin-5 metabolism, Intestinal Mucosa immunology, Intestinal Mucosa metabolism, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Necator americanus physiology, Necatoriasis parasitology, Necatoriasis pathology, Time Factors, Celiac Disease immunology, Duodenum immunology, Necator americanus immunology, Necatoriasis immunology
- 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.
- Published
- 2011
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