Enterocyte Microvillus-Derived Vesicles Detoxify Bacterial Products and Regulate Epithelial-Microbial Interactions

The continuous monolayer of intestinal epithelial cells (IECs) lining the gut lumen functions as the site of nutrient absorption and as a physical barrier to prevent the translocation of microbes and associated toxic compounds into the peripheral vasculature [1]. IECs also express host defense proteins such as intestinal alkaline phosphatase (IAP), which detoxify bacterial products and prevent intestinal inflammation [2–5]. Our laboratory recently showed that IAP is enriched on vesicles that are released from the tips of IEC microvilli and accumulate in the intestinal lumen [6, 7]. Here, we show that these native “lumenal vesicles” (LVs) (1) contain catalytically active IAP that can dephosphorylate lipopolysaccharide (LPS), (2) cluster on the surface of native lumenal bacteria, (3) prevent the adherence of enteropathogenic E. coli (EPEC) to epithelial monolayers, and (4) limit bacterial population growth. We also find that IECs upregulate LV production in response to EPEC and other Gram-negative pathogens. Together, these results suggest that microvillar vesicle shedding represents a novel mechanism for distributing host defense machinery into the intestinal lumen and that microvillus-derived LVs modulate epithelial-microbial interactions. ► Enterocyte microvillus-derived lumenal vesicles (LVs) detoxify bacterial toxins ► LVs bind directly to bacteria and prevent pathogenic attachment to epithelial cells ► LVs limit population growth of both commensal and pathogenic bacteria ► LV production is a constitutive process but is upregulated by bacterial stimulation