Project description:Commensal bacteria are crucial in maintaining host physiological homeostasis, immune system development, and protection against pathogens. Despite their significance, the factors influencing persistent bacterial colonization and their impact on the host still need to be fully understood. Animal models have served as valuable tools to investigate these interactions, but most have limitations. The bacterial genus Neisseria, which includes both commensal and pathogenic species, has been studied from a pathogenicity to humans’ perspective, but lacks models that study immune responses in the context of long-term persistence. Neisseria musculi, a recently described natural commensal of mice, offers a unique opportunity to study long-term host-commensal interactions. In this study, for the first time we have used this model to study the transcriptional, phenotypic, and functional dynamics of immune cell signatures in the mucosal and systemic tissue of mice in response to Neisseria musculi colonization. We found key genes and pathways vital for immune homeostasis in palate tissue, validated by flow cytometry of immune cells from lung, blood and spleen. This study offers a novel avenue for advancing our understanding of host-bacteria dynamics and may provide a platform for developing efficacious interventions against mucosal persistence by pathogenic Neisseria.
Project description:Suppression of chronic Arabidopsis immune responses is a widespread but typically strain-specific trait across the major bacterial lineages of the plant microbiota. Here, through phylogenetic analysis of 1,765 Xanthomonadales genomes, we show that immunomodulation is a highly conserved, ancestral trait across this core order of the plant microbiota, and preceded specialization of these bacteria as host-adapted pathogens. Rhodanobacter R179, from the deepest branch of the Xanthomonadales, activates immune responses which are dependent on EFR and SOBIR1 cell-surface receptor complexes, yet root transcriptomics suggest the commensal evades host recognition upon prolonged association. This commensal camouflage is likely due to the combined activities of the conserved ABC transporter permease (dssA) and the TonB-dependent transporter (dssB) and the selective elimination of immunogenic elicitors produced by R179, other microbiota members, and the plant host. The ability of R179 to mask itself and other commensals from host recognition is consistent with a convergence of distinct root transcriptomes triggered by immunosuppressive or non-suppressive synthetic communities upon R179 co-inoculation. Although root load of R179 on wild-type and efr fls2 sobir1 mutant plants was indistinguishable in mono-associations, immunomodulation through dssAB provided R179 with a competitive advantage in a community context in the absence of other immunosuppressive bacteria. Furthermore, root colonization of diverse commensal Xanthomonadales strains varied 1,000-fold without detrimental impacts on the host. We propose that conservation of immunomodulation by Xanthomonadales is related to their adaptation to terrestrial habitats and might have contributed to variation in strain-specific root association, which together accounts for their prominent role in plant microbiota establishment.
Project description:Here we directly compare for the first time how the longstanding static model of mouse Dentate Gyrus (DG) development compares with a comprehensive high-resolution live-cell multiphoton (live-MPM) imaging approach. We took advantage of multiple fluorescent protein-based cell-type specific reporters to identify Neural Stem Cells (NSC), Intermediate Neurogenic Progenitors (INPs), and Granule Neurons (GNs) to generate live 4D cellular datasets across embryonic, postnatal and adult ages. Live-MPM revealed that INPs and NSCs migrated long distances along multiple routes to seed the SGZ from multiple directions, and from mosaic progenitor zones along the septo-temporal axis of the hippocampus. We found that dynamic INPs processes and interactions contributed to the architecture of both transient and permanent NSC niches during embryonic development, and that INP cellular plasticity is maintained in the adult SGZ NSC niche. We also used a Molecular Systems (MS) approach to determine the basis for maintained INP cellular plasticity that revealed an overlapping signaling network infrastructure based largely on Rho-family mediated regulation of cytoskeletal dynamics. Our combined strategies revealed that dynamic INPs are a major molecular signaling transition state in the adult SGZ, and that Tbr2 expression defines the initial stage of GN commitment. Our novel findings reveal fundamental new insight into one of the most well studied brain regions key for normal cognitive function, and the importance of analyzing the development of live stem cell niches in vivo. In concert with live-cell imaging, we used microarray analysis to identify genes that may be involved in the development of the Dentate Gyrus NSC niche.
Project description:The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. The process by which the commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation, anti-microbial defenses, and tissue repair, and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Control of Th17 cell differentiation by SFB may thus establish a balance between optimal host defense preparedness and potentially damaging T cell responses. Manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease. Experiment Overall Design: We compared the gene expression profiles in the terminal ileum of Swiss-Webster GF mice before and after colonization with SFB, which induced robust Th17 cell differentiation. To sieve out host effects, the role of other microbiota, as well as other factors, we also evaluated the transcriptional program induced in Jackson C57BL/6 mice after co-housing with Taconic B6 animals, which also induces Th17 cell differentiation. 0.5 cm of the most distal part of the small intestine was dissected. Total RNA was extracted with TRIzol. RNA was labeled and hybridized to GeneChip Mouse Genome 430 2.0 arrays following the Affymetrix protocols. Data were analyzed in GeneSpring GX10.
Project description:The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. The process by which the commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation, anti-microbial defenses, and tissue repair, and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Control of Th17 cell differentiation by SFB may thus establish a balance between optimal host defense preparedness and potentially damaging T cell responses. Manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.
Project description:Host pathways mediating changes in immune states elicited by intestinal microbial colonization are incompletely characterized. Here we describe alterations of the host immune state induced by colonization of germ-free zebrafish larvae with an intestinal microbial community or single bacterial species. We show that microbiota-induced changes in intestinal leukocyte subsets and whole-body host gene expression are dependent on the innate immune adaptor gene myd88. Similar patterns of gene expression are elicited by colonization with conventional microbiome, as well as mono-colonization with two different zebrafish commensal bacterial strains. By studying loss-of-function myd88 mutants, we find that colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota-induced effects on myd88 transcription and intestinal immune cell composition.
2018-10-05 | GSE82200 | GEO
Project description:Conserved Genetic Basis for Microbial Colonization of the Gut