Project description:Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. We comprehensively identified the modulatory effects of phylogenetically diverse human gut microbes on the murine intestinal transcriptome. Gene-expression profiles were generated from the whole-tissue intestinal RNA of mice colonized with various single microbial strains. The selection of microbe-specific effects, from the transcriptional response, yielded only a small number of transcripts, indicating that symbiotic microbes have only limited effects on the gut transcriptome overall. Moreover, none of these microbe-specific transcripts was uniformly induced by all microbes. Interestingly, these responsive transcripts were induced by some microbes but repressed by others, suggesting different microbes can have diametrically opposed consequences.
Project description:Regulatory T cells (Tregs) are immune cells that play a crucial role in maintaining tolerance to harmless antigens, including commensal microbes. In the intestine, Tregs can be classified into subsets based on their expression of transcription factors Helios, Rorg, Gata3 and cMaf. The exact functions of the intestinal Treg subsets and their role in maintaining tolerance to intestinal microbes is not fully understood. Here, we generated conditional knockout mice of each Treg subset and profiled the composition of their intestinal microbiota by performing 16S rRNA sequencing of stool from conditional knockouts and matched littermate controls.
Project description:Intestinal T cells responses are strongly influenced by microbes. In this study we aimed to adress how different microbes and what microbial factors influce intestinal T cells differentiation and subsequent clonal expansion. Paticularly we choose Clostridium ramosum (Cr) as a strong induced of a subest of intestinal Tregs (Rorc+), a medium inducer or Rorc+ Tregs an T1h7 Escherichia coli Nissle (EcN) and a strain that did not impact either o those cell (Pm). In addition, to study the impact of Escherichia coli Nissle (EcN) ploysaccharide K5 capsule on intestinal T cells activation, we used a EcN strain lacking the K5 capsule (kfiCD). At day 21 post-monocolonization we isolated CD4 T cells from monocolonized mice in both intestinal Lamina Propria and spleen and performed single cells RNA and TCR seq.