Piliation of Lactobacillus rhamnosus GG promotes adhesion, phagocytosis, and cytokine modulation in macrophages.

Recently, spaCBA-encoded pili on the cell surface of Lactobacillus rhamnosus GG were identified to be key molecules for binding to human intestinal mucus and Caco-2 intestinal epithelial cells. Here, we investigated the role of the SpaCBA pilus of L. rhamnosus GG in the interaction with macrophages in vitro by comparing the wild type with surface mutants. Our results show that SpaCBA pili play a significant role in the capacity for adhesion to macrophages and also promote bacterial uptake by these phagocytic cells. Interestingly, our data suggest that SpaCBA pili also mediate anti-inflammatory effects by induction of interleukin-10 (IL-10) mRNA and reduction of interleukin-6 (IL-6) mRNA in a murine RAW 264.7 macrophage cell line. These pili appear to mediate these effects indirectly by promoting close contact with the macrophages, facilitating the exertion of anti-inflammatory effects by other surface molecules via yet unknown mechanisms. Blockage of complement receptor 3 (CR3), previously identified to be a receptor for streptococcal pili, significantly decreased the uptake of pilus-expressing strains in RAW 264.7 cells, while the expression of IL-10 and IL-6 mRNA by these macrophages was not affected by this blocking. On the other hand, blockage of Toll-like receptor 2 (TLR2) significantly reduced the expression of IL-6 mRNA irrespective of the presence of pili.

Novel opportunities for the exploitation of host-microbiome interactions in the intestine.

New sequencing technologies have dramatically increased our knowledge on the composition of the human intestinal microbiota in health and disease. In parallel, various omics as well as focused molecular studies have revealed novel insights in host-microbiome interactions at the cellular and molecular level. Although these studies are mainly descriptive, advanced microbiota-targeting intervention strategies are being explored, ranging from the selection of novel probiotic strains and synthetic stool substitutes, toward the better monitoring of prebiotic and dietary interventions. It can be envisaged that the efficacy of microbiota interventions will depend on the status of the microbiota of an individual at baseline, but also on genetic and physiological host parameters that determine the capacity to interact with microbes via specific receptors.