TY - JOUR
T1 - Differential changes in expression of intestinal antimicrobial peptide genes during ascarislumbricoides infection in zambian adults do not respond to helminth eradication
AU - Kapulu, Melissa C.
AU - Simuyandi, Michelo
AU - Sianongo, Sandie
AU - Mutale, Mubanga
AU - Katubulushi, Max
AU - Kelly, Paul
PY - 2011/5/15
Y1 - 2011/5/15
N2 - Background. Intestinal helminthiasis modulates immune responses to vaccines and environmental allergens. To explore the impact on intestinal host defense, we assessed expression of antimicrobial peptide genes, together with T cell subset markers and cytokines, in patients with ascariasis before and after treatment. Methods. Case patients (n=27) and control subjects (n=44) underwent enteroscopy for collection of jejunal biopsy specimens, which were used in quantitative, real-time reverse-transcription polymerase chain reaction for a range of host defense genes; blood samples were also analyzed simultaneously. Results. The level of gene expression (mRNA) of HD5, hBD1, and LL-37 was lower in case patients than in control subjects, and the level of expression of HD6 was increased. However, after successful eradication, there was no trend to values seen in control subjects. Helminthiasis was associated with increased intestinal expression of the Th1 genes T-bet and interferon-γ. In peripheral blood mononuclear cells (PBMCs), a mixed profile of T cell markers and cytokines was increased. Ascaris-induced down-regulation of HD5 was observed in individuals with higher RORγt expression in PBMCs, but we found no evidence that this was mediated by circulating interleukin-22. Conclusions. Human ascariasis was associated with changes in antimicrobial peptide gene expression and immunological markers. Such changes may have implications for susceptibility to infectious disease and responsiveness to oral vaccines in tropical populations.
AB - Background. Intestinal helminthiasis modulates immune responses to vaccines and environmental allergens. To explore the impact on intestinal host defense, we assessed expression of antimicrobial peptide genes, together with T cell subset markers and cytokines, in patients with ascariasis before and after treatment. Methods. Case patients (n=27) and control subjects (n=44) underwent enteroscopy for collection of jejunal biopsy specimens, which were used in quantitative, real-time reverse-transcription polymerase chain reaction for a range of host defense genes; blood samples were also analyzed simultaneously. Results. The level of gene expression (mRNA) of HD5, hBD1, and LL-37 was lower in case patients than in control subjects, and the level of expression of HD6 was increased. However, after successful eradication, there was no trend to values seen in control subjects. Helminthiasis was associated with increased intestinal expression of the Th1 genes T-bet and interferon-γ. In peripheral blood mononuclear cells (PBMCs), a mixed profile of T cell markers and cytokines was increased. Ascaris-induced down-regulation of HD5 was observed in individuals with higher RORγt expression in PBMCs, but we found no evidence that this was mediated by circulating interleukin-22. Conclusions. Human ascariasis was associated with changes in antimicrobial peptide gene expression and immunological markers. Such changes may have implications for susceptibility to infectious disease and responsiveness to oral vaccines in tropical populations.
UR - http://www.scopus.com/inward/record.url?scp=79954996812&partnerID=8YFLogxK
U2 - 10.1093/infdis/jir035
DO - 10.1093/infdis/jir035
M3 - Article
SN - 0022-1899
VL - 203
SP - 1464
EP - 1473
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -