Antimicrobial host defense in the upper gastrointestinal tract

Aims: With the exception of fungi, microbial infections are rare in the esophagus. Herein, we aimed to systematically assess the distribution and quantity of different antimicrobial host factors as well as, for the first time, functional mucosal antimicrobial activity in the upper gastrointestinal tract.

Methods: We investigated biopsies from the healthy esophagus, 3 different locations in the stomach and the duodenum in a total of 32 individuals. Using real-time-PCR with external standards, we compared absolute expression of mRNA encoding antimicrobial peptides including defensins, cathelicidin, bactericidal/permeability-increasing protein (BPI), psoriasin and elafin. In addition, we performed immunostaining for human-beta-defensin-1 (HBD-1), elafin and psoriasin. To test functional relevance, we assessed antimicrobial activity of cationic extracts from biopsies against E. coli ATCC 25922 and a clinical isolate of Candida albicans.

Results: In contrast to HBD1 which was similarly expressed in all tissues, inducible β-defensins in the healthy esophagus were much higher compared to the stomach and duodenum (for HBD2–4: p<0.01). In addition, the antiproteases elafin and psoriasin were also predominantly expressed in the esophagus (p<0.005). In contrast, LL-37 and BPI were only minimally expressed. Cationic tissue extracts from both, the esophagus as well as the stomach showed potent antibacterial activity against E. coli. Consistent with susceptibility to Candida infection, the esophageal extracts exhibited a weaker activity against Candida albicans (p=0.026).

Conclusion: Despite dominant expression of antimicrobial host peptides, esophageal tissue shows a weakened potency to kill Candida albicans which could explain preferential infection by this fungus. These data suggest an important role of yet unknown antimicrobial molecules, especially in the stomach.