Suppression of adaptive immunity by Borrelia burgdorferiin the murine host

Abstract

Abstract Borrelia burgdorferi (Bb), the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enable it to persist chronically. These strategies include complement inhibition, antigenic variation, and suppression of adaptive immunity. Previous studies have shown that lymph node (LN) germinal centers generated in response to Bb collapse one-month post-infection. The resulting immune response is characterized by unusually strong IgM production and a lack of long-lived immunity. Here we aimed to better characterize how Bb manipulates host immunity, ultimately resulting in failure to clear the infection. Mice infected with Bb and concomitantly immunized with recombinant SARS-CoV-2 spike protein had an abrogated antibody response to the immunization. To test how long this humoral immune suppression lasts, mice were immunized at 2-, 4-, and 6-weeks post Bb infection. Suppression of host antibody production against SARS-CoV-2 spike protein peaked at 2 weeks post Bb infection but continued for all timepoints measured. We also examined changes to gene expression in murine LNs 15 days post-infection using RT-qPCR and found that live Bb, but not heat-killed 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. In addition, both Il2 and Il2ra were downregulated, which is typically observed during the resolution of infection and indicates a potential lack of antigenic restimulation. These data suggest Bb may disrupt T cell responses, which could play a role in the failure to mount an appropriate humoral immune response. Funding for this work was provided by UNTHSC.