Active suppression of adaptive immunity by Borrelia burgdorferi in the murine host

Purpose: Borrelia burgdorferi(Bb), the spirochetal agent of Lyme disease, utilizes a variety of tactics to evade and suppress the host immune response which enable it to persist chronically. These tactics can include complement inhibition, antigenic variation, extracellular matrix degradation, and adaptive immune suppression. Adaptive immune suppression by Bb is still not well understood. Previous studies have shown that lymph node (LN) germinal centers generated in response to Bb collapse one-month post-infection. The resulting humoral immune response is characterized by unusually strong and persistent IgM production and lack of long-lived immunity. Here we aimed to better characterize how Bb manipulates the host humoral immune response, ultimately resulting in failure to clear the infection. Methods: Mice were infected with Bb and concomitantly immunized with recombinant SARS-CoV-2 spike protein to measure the antibody response to the immunization and how it may be dampened by infection with Bb. We also immunized mice at 2-, 4-, and 6-weeks post-infection to test how long this humoral immune suppression lasts. Using RT-qPCR, we also examined changes to gene expression in murine LNs 15 days post-infection to better characterize what may be causing this observed immune dysfunction. Results: Suppression of host antibody production against the rSARS-CoV-2 spike protein peaked at 2 weeks post-infection but continued for all timepoints measured. We also found that live Bb, but not heat-killed (HK) Bb, broadly suppressed many genes related to T cell homing and function. Genes which play a critical role in the establishment and maintenance of T cell zones within the LNs, Ccl19 and Ccr7, were significantly downregulated. This was interesting considering previous studies have provided evidence of disorganization of LN architecture and the disruption of T cell zones beginning around 10 days post-infection. In addition, both Il2 and Il2ra were significantly downregulated, which is typically observed during the resolution of infection and indicates a lack of antigenic restimulation. Conclusion: These data suggest potential T cell disruption by Bb, which may play a role in the failure to mount an appropriate humoral immune response to the infection.