UC Davis

Host immune responses and the host immune system itself are shaped by interactions with environmental factors including diet, commensal microbiota, and pathogens. The microbiome, defined as a community of microorganisms and their interactions with their surrounding environmental conditions, further interacts with structural elements, metabolites, and signaling molecules from other microorganisms and the host. These networks of interactions result in heterogeneous immune responses and affect our ability to develop immunotherapies or vaccines that are universally applicable to the entire population. Untangling these interactions between environmental factors and the host immune system in the presence of many covariates has been difficult but has been increasingly aided by advances in technologies and our ability to process multi-dimensional data sets. Understanding the extent of environmental influence on the host immune system is important to further identify the important factors to drive desired immune responses, especially for developing cancer therapies and vaccines. In this dissertation, we used metagenomics, transcriptomics, and single-cell immunophenotyping methods to understand important influences on the immune system, including diet, microbiome, latent viral infections, and viral vector-based vaccination. We found that dietary intervention can lead to transient changes in the gut microbiome without causing dramatic changes to the infant immune system, suggesting limited effects of host-microbe interactions over a short time period. Latent viral infections have much greater impacts on the host immune system and can additionally subvert or supplant relationships between the host and other microbes. Latent viral infections also resulted in different vaccine responses that can be observed at the transcriptomic level. Overall, we identified latent infection with cytomegalovirus (CMV) as one of the major contributors to different immune responses in different individuals, using rhesus macaque as an animal model. Future work targeting pathways changed by CMV may be important for understanding heterogeneous immune responses and for further development of CMV-based vaccine vectors.