Climate-Driven Immune Gene Expression Profiles in <i>Peromyscus leucopus</i> : Implications for Bacterial Infection Dynamics

Abstract<i>Peromyscus leucopus</i> mice, a primary reservoir for <i>Borrelia burgdorferi</i> (the causative agent of Lyme disease), are a valuable system for examining climate-driven variation in host immunity. Particularly under rapid climate change, immune variation among individual hosts might be critical in shaping disease dynamics, and understanding host competence is essential for predicting disease outbreaks and infection dynamics. We assessed the expression of six immune-related genes-toll-like receptor 2 (<i>TLR-2</i>), interferon gamma (<i>IFN-γ</i>), interleukin 6 (<i>IL-6</i>), interleukin 10 (<i>IL-10</i>), GATA-binding protein 3 (<i>GATA3</i>), and transforming growth factor beta (<i>TGF-β</i>)-broadly involved in pathogen recognition, elimination, and disease mitigation in ear biopsies from wild <i>P. leucopus</i> collected at eight National Ecological Observatory Network sites spanning 1,400 km across climatic gradients in the midwestern and northeastern United States. A principal component analysis identified two dimensions of gene expression. Principal component 1 included <i>TLR-2</i>, <i>IFN-γ</i>, <i>IL-6</i>, and <i>IL-10</i>, genes associated with rapid immune activation and regulation, suggesting a role in enhancing immune readiness and potentially increasing host resistance by reducing pathogen burden. Principal component 2, composed of <i>GATA3</i> and <i>TGF-β</i>, comprised genes linked to parasite tolerance and tissue protection, which may help minimize immunopathology. Principal component 1 gene expression significantly increased in warmer, wetter climates, suggesting that enhanced immune readiness may facilitate resistance in such conditions. Our findings suggest that climate influences immune variation among individuals in <i>P. leucopus</i>, potentially affecting host competence. However, these gene expression profiles are not direct evidence of resistance or tolerance. Further research should explicitly link gene expression patterns to pathogen infection and disease transmission dynamics to clarify their ecological and epidemiological significance.