Project description:Laboratory mice comprise an inexpensive and expeditious model organism for preclinical vaccine testing; however, vaccine immunogenicity often fails to adequately translate to humans. Recent reports indicate that reconstituting physiologic microbial experience to specific pathogen free (SPF) mice induces durable immunological changes that better recapitulate the human immune system. We examined the impact of microbial experience on responses to vaccination after cohousing laboratory mice with pet store mice. We demonstrate that human transcriptional responses to influenza vaccination are better recapitulated in cohoused mice. Induction of humoral responses by vaccination was dampened in cohoused mice and resulted in poor control upon challenge. Additionally, the establishment of protective heterosubtypic T cell immunity was compromised in cohoused mice. In summary, SPF mice exaggerated both humoral and T cell protection induced by influenza vaccines compared to cohoused mice, suggesting that reconstituting microbial experience in laboratory mice through cohousing may better inform preclinical vaccine testing.
Project description:Transcriptional analysis of immunological characteristics of petstore mice, C57Bl/6 laboratory mice, and C57Bl/6 laboratory mice cohoused with petstore. We hypothesized that cohousing would confer a basal transcriptional signature of immune activation to laboratory mice from petstore mice. Comparison of these data with existing human adult vs. neonatal PBMC expression profiling data (GSE27272) revealed close concordance of laboratory mice with human neonates, and of cohoused or petstore mice with human adults. Results highlight the impact of environment on the basal immune state and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans. Total RNA was isolated from PBMC of C57Bl/6 laboratory mice, petstore mice and C57Bl/6 laboratory mice cohoused with petstore mice (at least after 60 days post-cohousing)and transcriptional comparison among 3 groups were performed.
Project description:Transcriptional analysis of immunological characteristics of petstore mice, C57Bl/6 laboratory mice, and C57Bl/6 laboratory mice cohoused with petstore. We hypothesized that cohousing would confer a basal transcriptional signature of immune activation to laboratory mice from petstore mice. Comparison of these data with existing human adult vs. neonatal PBMC expression profiling data (GSE27272) revealed close concordance of laboratory mice with human neonates, and of cohoused or petstore mice with human adults. Results highlight the impact of environment on the basal immune state and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans.
Project description:Gut microbes elicit specific changes in gene expression in the colon of mice. We colonized germ-free mice with microbial communities from the guts of humans, zebrafish and termites, human skin and tongue, soil and estuarine microbial mats. We used microarrays to detail the differences in global gene expression in colon tissue that are caused by the different microbial communities 28 days after gavage into the germfree animal. Three biological replicates per group, male C57BL/6 mice (12-16 weeks old)
Project description:Gut microbes elicit specific changes in gene expression in the colon of mice. We colonized germ-free mice with microbial communities from the guts of humans, zebrafish and termites, human skin and tongue, soil and estuarine microbial mats. We used microarrays to detail the differences in global gene expression in colon tissue that are caused by the different microbial communities 28 days after gavage into the germfree animal.
Project description:The immune system of SPF mice is dominated by naïve phenotype immune cells, especially within the T cell compartment, and resembles that of neonatal humans (Beura et al., 2016; Reese et al., 2016). Sequential infection of SPF-housed laboratory mice with common experimental pathogens, such as MHV, MCMV, Listeria monocytogenes, LCMV, and influenza A virus (Berton et al., 2022; Reese et al., 2016), or cohousing (CoH) SPF mice with pet store mice carrying multiple pathogenic and commensal bacteria, viruses, and/or fungi (Beura et al., 2016) induces immune system alterations and maturations that more closely resemble the adult human immune system. Such microbial exposure drastically alters the composition and function of the immune system of laboratory mice, which can significantly influence the overall outcome (and survival) to subsequent infection. Here we report CD11b+ CD115+ monocytes sorted from female specific pathogen-free (SPF) C57BL/6N (B6) mice co-housed with petstore mice for 60 days are transcriptionally different than SPF CD11b+ CD115+ monocytes
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as Crohn’s disease and colorectal cancer. Our data showed that Nod2-mediated risk of intestinal inflammation in colitis model is communicable to WT mice by cohousing. Here, we investigated if Nod2-deficient mice microbiota is able to change transcript profiles in Nod2-immunocompetent mice (C57Bl6/J mice) independently of colitis.
Project description:Tibet is one of the most threatened regions by climate warming, thus understanding how its microbial communities function may be of high importance for predicting microbial responses to climate changes. Here, we report a study to profile soil microbial structural genes, which infers functional roles of microbial communities, aiming to explore potential microbial responses to climate changes via a strategy of space-for-time substitution. Using a microarray-based metagenomics tool named GeoChip 4.0, we showed that microbial communities were distinct for most but not all of the sites. Substantial variations were apparent in stress, N and C cycling genes, but they were in line with the functional roles of these genes. sixty-three samples were collected from four elevations (3200,3400,3600 and 3800 m) along a Tibetan alpine meadow; Three replicates in each treatment
Project description:Functional redundancy in bacterial communities is expected to allow microbial assemblages to survive perturbation by allowing continuity in function despite compositional changes in communities. Recent evidence suggests, however, that microbial communities change both composition and function as a result of disturbance. We present evidence for a third response: resistance. We examined microbial community response to perturbation caused by nutrient enrichment in salt marsh sediments using deep pyrosequencing of 16S rRNA and functional gene microarrays targeting the nirS gene. Composition of the microbial community, as demonstrated by both genes, was unaffected by significant variations in external nutrient supply, despite demonstrable and diverse nutrient–induced changes in many aspects of marsh ecology. The lack of response to external forcing demonstrates a remarkable uncoupling between microbial composition and ecosystem-level biogeochemical processes and suggests that sediment microbial communities are able to resist some forms of perturbation.
Project description:To effectively monitor microbial populations in acidic environments and bioleaching systems, a comprehensive 50-mer-based oligonucleotide microarray was developed based on most of the known genes associated with the acidophiles. This array contained 1,072 probes in which there were 571 related to 16S rRNA and 501 related to functional genes. Acid mine drainage (AMD) presents numerous problems to the aquatic life and surrounding ecosystems. However, little is known about the geographic distribution, diversity, composition, structure and function of AMD microbial communities. In this study, we analyzed the geographic distribution of AMD microbial communities from twenty sites using restriction fragment length polymorphism (RFLP) analysis of 16S rRNA genes, and the results showed that AMD microbial communities were geographically distributed and had high variations among different sites. Then an AMD-specific microarray was used to further analyze nine AMD microbial communities, and showed that those nine AMD microbial communities had high variations measured by the number of detected genes, overlapping genes between samples, unique genes, and diversity indices. Statistical analyses indicated that the concentrations of Fe, S, Ca, Mg, Zn, Cu and pH had strong impacts on both phylogenetic and functional diversity, composition, and structure of AMD microbial communities. This study provides insights into our understanding of the geographic distribution, diversity, composition, structure and functional potential of AMD microbial communities and key environmental factors shaping them. This study investigated the geographic distribution of Acid Mine Drainages microbial communities using a 16S rRNA gene-based RFLP method and the diversity, composition and structure of AMD microbial communities phylogenetically and functionally using an AMD-specific microarray which contained 1,072 probes ( 571 related to 16S rRNA and 501 related to functional genes). The functional genes in the microarray were involved in carbon metabolism (158), nitrogen metabolism (72), sulfur metabolism (39), iron metabolism (68), DNA replication and repair (97), metal-resistance (27), membrane-relate gene (16), transposon (13) and IST sequence (11).