Intestinal defensin gene expression in human populations

Defensins are thought to play a major role in the defence of small intestinal crypts against colonisation by potential pathogens. In humans two alpha-defensins, HD5 and HD6 and two beta-defensins, hBD1 and hBD2, probably contribute to the antimicrobial barrier, but there are no data to indicate how the expression of these defensin genes might vary in individuals and in populations. To begin to address this question we developed a competitive reverse transcriptase polymerase chain reaction (RT-PCR) assay to quantify HD5 and HD6 mRNA and used it to measure transcripts in small intestinal biopsy tissue from adults living in London, UK, or in Lusaka, Zambia. We also measured alpha- and beta-defensin mRNA in biopsies collected in London from different regions of the small intestine. Jejunal biopsies (n=169) from 83 adults in Lusaka contained approximately one order of magnitude less HD5 and HD6 mRNA than biopsies (n=33) obtained from 27 adults in London. HD5 and HD6 transcript levels were high throughout duodenum, jejunum and ileum. hBD1 and hBD2 mRNA were detected in some, but not all, biopsies from normal small intestine. These data suggest that alpha-defensin expression is down-regulated in tropical populations, and that there are distinct pathways regulating transcription of alpha- and beta-defensins.