RNAseqcharacterization ofB. burgdorferi-inducedinnate immune memoryandregulation ofLyme carditis through Acod1

Borrelia burgdorferi (Bb), which causes Lyme disease, establishes long term infection and leads to disease manifestations that are mostly a result of host immune responses to the pathogen. Disease symptoms often resolve without treatment, suggesting innate immune memory may play a role in dampening inflammation over time. We used an in vitro model of repeated stimulations in macrophage and performed RNA sequencing on acute and memory states. We categorized differentially expressed genes based on their response to acute infection as well as their memory response compared to acute. We discuss four expression subsets representing important cellular changes to repeated stimulation and focus on genes that are negative regulators of inflammation induced during the acute phase and mediate long-term immunosuppression. We identified Aconitate decarboxylase 1 (Acod1), a negative regulator of inflammatory responses, and confirmed its role during in vivo long-term infection with Bb, with a specific role in Lyme carditis. Mouse Bone marrow derived macrophages were either left unstimulated, stimulated at 6 hours with Borrelia burgdorferi or stimulated at both 6 and 24 hours