Abstract
Intestinal bacteria have diverse and complex influence on their host. Evidence is accumulating that this may be mediated in part by bacterial extracellular membrane vesicles (MV), nanometer-sized particles important for intercellular communication. Little is known about the composition of MV from gram-positive beneficial bacteria nor how they interact with intestinal epithelial cells (IEC). Here we demonstrate that MV from Lacticaseibacillus rhamnosus JB-1 are endocytosed in a likely clathrin-dependent manner by both mouse and human IEC in vitro and by mouse IEC in vivo. We further show that JB-1 MV contain lipoteichoic acid (LTA) that activates Toll-like receptor 2 (TLR2) and induces immunoregulatory interleukin-10 expression by dendritic cells in an internalization-dependent manner. By contrast, neither LTA nor TLR2 appear to be required for JB-1 MV endocytosis by IEC. These results demonstrate a novel mechanism by which bacterial MV can influence host physiology and suggest one potential route for beneficial influence of certain bacteria and probiotics.
Highlights
Intestinal microbes have complex bidirectional relationships with their host
We show that membrane vesicles (MV) from JB-1 are endocytosed in a likely clathrin-mediated manner by both mouse and human intestinal epithelial cells (IEC) lines in vitro and by mouse IEC in vivo, using outer membrane vesicles (OMV) from Escherichia coli Nissle 1917 (EcN) as a positive control as they are known to be endocytosed by IEC23
Most work far has examined the role of MV in pathogenic effects of especially gram-negative bacteria[25], while more recent work has considered the interaction between intestinal epithelial cells and MV from beneficial bacteria
Summary
Intestinal microbes (microbiota) have complex bidirectional relationships with their host. Currently understudied in this context, involves extracellular vesicles, membrane-bound nanoparticles that are ubiquitously produced by both prokaryotes and e ukaryotes[7] In bacteria, these are often referred to as microvesicles or membrane vesicles (MV), or outer membrane vesicles (OMV) in the case of gram-negative bacteria. Bacteria express conserved features (microbe-associated molecular patterns; MAMPs) that are recognized by pattern recognition receptors (PRRs) of many host cells, including epithelial, endothelial, and immune[21]. These MAMPs are thought to be important signalling molecules present on MV, which can modulate responses in host intestinal epithelial cells (IEC) and immune cells[9] and may be involved in their immunoregulatory influence. Our data suggest that internalization of JB-1 MV by DCs is involved in their induction of IL-10 expression
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