Project description:This SuperSeries is composed of the following subset Series: GSE11944: Mucosal Glycan Foraging Enhances the Fitness and Transmission of a Saccharolytic Human Distal Gut Symbiont GSE11953: Mucosal Glycan Foraging Enhances the Fitness and Transmission of a Saccharolytic Human Distal Gut Symbiont: ECF mutant GSE11962: Growth of B. thetaiotaomicron on purified host mucosal glycans and glycan fragments Refer to individual Series
Project description:The role of mucosal invariant T (MAIT) cells in the lung tumor microenvironment re-mains poorly understood, especially in the setting of immune checkpoint inhibitors. We identified intratumoral MAIT cells from paired single cell RNA and TCR sequencing datasets of tumor infil-trating CD3 T cells isolated from non-small cell lung cancer tumors in patients receiving neoadju-vant PD-1 blockade therapy. MAIT cells were subclustered to identify conventional MAIT-associ-ated TCR clonotypes, which were then tested for the recognition of bacteria using a MAIT TCR capture functional assay. Strikingly, surveillance of intratumoral bacteria in lung cancer patients revealed Enterococcus spp. that are not directly recognized by MAIT cells but, nevertheless can synergize with exogenous riboflavin biosynthesis-derived metabolites to induce expression of MR1 by antigen presenting cells (APC, dendritic cells, B cells and mononuclear phagocytes). Enhanced MR1 cell surface expression resulted from enterococcal-mediated perturbation of an endo-lysosomal vacuolar pathway with recycling of early endosomal MR1 to the APC cytoplasmic membrane. Riboflavin auxotrophic Enterococcus spp may therefore exercise their beneficial im-munomodulatory functions upon immune checkpoint blockade treatment, at least in part, by pro-moting intratumoral MR1 expression and innate-like T cell activation. Our results indicate that composition of the intratumoral microbiome during immune checkpoint inhibitor treatment has the potential to impact the function of human intratumoral MAIT cells.
Project description:Gene expression profiles of Bacteroides thetaiotaomicron in vitro during growth on host mucosal polysaccharides as sole carbon sources. All substrates in this series are derived from porcine gastric mucin and include mucin O-glycans and glycosaminoglycans. Two different culture formats used: 800ml batch-culture bioreactors and 5ml tube cultures (format is indicated within each sample title). Each set of growths was referenced to a minimal medium glucose reference corressponding to the same culture format. Unfractionated porcine mucosal glycan (PMG) growths were compared to previously published in vivo datasets, which were referenced to the 800ml minimal medium glucose reference dataset.
Project description:To systematically characterize the phenotypic behavior of two 'prototrophic' version of the Yeast Knockout (YKO) gene deletion collection, we compared genome-wide finess assays across a diverse set of drug and environmental conditions. This analysis uncovered experimental liabilities in the the prototrophic collections distinct from the YKO auxotrophies that shows that auxotrophic repair (regardless of methodology) does not restore wildtype behaviour.
Project description:Gene expression profiles of Bacteroides thetaiotaomicron in vitro during growth on host mucosal polysaccharides as sole carbon sources. All substrates in this series are derived from porcine gastric mucin and include mucin O-glycans and glycosaminoglycans.
Project description:Synergistic role of riboflavin-auxotrophic Enterococcus for MR1 expression and in-tra-tumoral mucosal associated invariant T (MAIT) cell activation