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.
2016-03-09 | GSE78979 | GEO
Project description:studies of gut microbial diversity on hyperuricemia mice