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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Biopsy
-
CD4 Antigens / immunology
-
CD4 Antigens / metabolism
-
Celiac Disease / immunology*
-
Celiac Disease / parasitology
-
Celiac Disease / pathology
-
Cells, Cultured
-
Clinical Trials as Topic
-
Duodenum / immunology*
-
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 / immunology*
-
Necator americanus / physiology
-
Necatoriasis / immunology*
-
Necatoriasis / parasitology
-
Necatoriasis / pathology
-
Time Factors
Substances
-
CD4 Antigens
-
FOXP3 protein, human
-
Forkhead Transcription Factors
-
Interleukin-17
-
Interleukin-2
-
Interleukin-2 Receptor alpha Subunit
-
Interleukin-5
-
Interferon-gamma
-
Gliadin