Macrophage training to Borrelia burgdorferi governs cardiac inflammation in the mammalian host [RNA-seq]

Macrophage exposure to vaccine or vaccine-like formulations results in disparate secondary responses. We have identified the transcriptomic and metabolic changes associated with the memory response of macrophages to Borrelia burgdorferi, an extracellular pathogen able to establish long-term infections in mammals. Memory macrophages show an enhanced ability to bind and internalize the spirochete with decreased inflammatory responses, in part regulated by Irf4. Experienced macrophages also show an augmented glycolytic output. In vivo, glycolysis inhibition results in decreased cardiac inflammation and reduced expression of Irf4. Our data show that B. burgdorferi induces long-term, memory-like responses that are amenable to be manipulated in vivo. Genome-wide changes in gene Expression in mouse bone marrow-derived macrophages stimulated and restimulated with Borrelia burgdorferi at a multiplicity of infection of 25. Groups corresponding to unstimulated (U) or previously stimulated and washed (B) macrophages, either left unstimulated (UU, BU) or restimulated with B. burgdorferi (UB, BB) were generated by RNAseq.