Innate Immune Memory to Repeated Exposure Correlates with Murine In Vivo Inflammatory Phenotypes.

, the causative agent of Lyme disease, is transmitted by the bite of an infected tick. Once inoculated into the host dermis, it disseminates to various organs including distant skin sites, the heart, the joint and the nervous system. Most humans will develop an early skin manifestation called erythema migrans at the tick bite site. This can be followed by symptoms such as carditis, neuritis, meningitis, or arthritis if not treated. A specific mouse strain, C3H/HeN develops arthritis with infection whereas another strain, C57BL/6, develops minimal to no arthritis. Neither strain of mice show any skin signs of rash or inflammation. Factors that determine the presence of skin inflammation and the joint arthritis susceptibility in the host are only partially characterized. We show in this study that murine fibroblast-like synoviocytes display trained immunity, a program in some cells that results in increased inflammatory responses if the cell has previously come in contact with a stimulus, and that trained immunity in fibroblast-like synoviocytes tested ex vivo correlates with Lyme arthritis susceptibility. Conversely, skin fibroblasts do not exhibit trained immunity, which correlates with the absence of skin symptoms in these mice. Moreover, we demonstrate that the trained phenotype in FLS is affected by the cell environment, which depends on the host genetic background. Future studies expanding this initial report of the role of trained immunity on symptoms of infection may provide insight into the pathogenesis of disease in murine models.