THE INFLUENCE OF HOUSING ENVIRONMENT ON THE MURINE INFLAMMATORY IMMUNE RESPONSE

PhDStudies have demonstrated the immune system to be significantly more plastic than previously believed. Multiple external factors have been shown to influence the immune response including alterations to the host’s external environment and psychological status. This thesis details an investigation of this influence; exposing male CD1 mice to a two-week environmental enrichment paradigm then subjecting them to one of a range of inflammatory disease models chosen to assess a specific aspect of their immune function. Enriched animals were found to possess significantly higher numbers of circulating innate leukocytes compared to those animals housed in a standard lab environment. This leukocytosis was found to persist when animals were subject to a model of zymosan-induced peritonitis, where enriched animals presented an enhanced neutrophil and macrophage influx into their peritoneal cavity. Similar results were observed in a model of sepsis induced by caecal ligation and puncture where enriched animals were also found possess an enhanced capacity for systemic bacterial clearance. Across both experiments no changes in inflammatory cytokine expression were observed between enriched and standard environment animals. Genomic and proteomic profiling supported these findings, revealing the increased expression of immune-modulatory genes associated with a heightened immune and moderated inflammatory response. Ex vivo analysis of leukocytes extracted from enriched animals showed they also possessed enhanced phagocytic function and an accompanying reduction in gene expression associated with heightened cytotoxic function. When subject to a model of persistent inflammation induced by sponge implantation, enriched animals again presented heightened leukocyte infiltration to the point of immune insult. This was accompanied with a reduction in the release of pro-inflammatory cytokines and the heightened expression of genes associated with a pro-resolving, wound healing phenotype. This study provides novel insights into the mechanisms by which environmental modulation may influence the immune response and of the potentially immune-protective influence of environmental enrichment.Medical Research Council and Queen Mary University of Londo