Borrelia burgdorferi is the causative agent of Lyme disease in humans, and susceptibility to it varies widely within a population, a phenomenon also observed in mice. Different mouse strains were used to understand the differences and similarities between disease susceptibility and resistance in human populations. The C3H/HeN mouse strain is the most susceptible, whereas the C57BL/6 strain is most resistant to Lyme Borreliosis. There are several factors associated with the differential disease phenotype, and one of the major determining factors is the IL-10 production between the mice strains. C3H/HeN mice and macrophages (MΦ) isolated from them do not produce adequate IL-10 in response to B. burgdorferi; instead they produce genes belonging to interferon response factors. We found that C3H/HeN MΦ harbored less cAMP in their cytoplasm, and the addition of exogenous cAMP converts their phenotype closer to resistant MΦs isolated from C57/BL6 mice. Currently, my research focuses on the evaluation of the role of cAMP in modulating epigenetic landscape of disease susceptibility and resistance genes, including IL-10.