title: Differential changes in expression of intestinal antimicrobial peptide genes during Ascaris lumbricoides infection in Zambian adults do not respond to helminth eradication.
abstract: 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.
authors.affiliation: Biological Sciences Department, School of Natural Sciences, University of Zambia, Lusaka.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Kapulu
authors.forename: Michelo
authors.initials: M
authors.lastname: Simuyandi
authors.forename: Sandie
authors.initials: S
authors.lastname: Sianongo
authors.forename: Mubanga
authors.initials: M
authors.lastname: Mutale
authors.forename: Max
authors.initials: M
authors.lastname: Katubulushi
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
mesh_terms: D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D001196:Ascariasis / Q000188:drug therapy* / Q000378:metabolism*; D017164:Ascaris lumbricoides; D015415:Biomarkers; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000502:physiology; D055815:Young Adult; D015024:Zambia / Q000453:epidemiology; D000098815:T-bet Transcription Factor
chemical_list: D000871:Anthelmintics; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D016207:Cytokines; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma