Master student Johns Hopkins Bloomberg Sch. of Pub. Hlth. BALTIMORE, Maryland, United States
Introduction/Rationale: Borrelia burgdorferi (Bb), the causative agent of Lyme disease, causes persistent infections in their reservoir hosts, including mice. B cell responses to Bb can control disease but cannot clear infection. Prior work in the lab identified a rapid collapse of infection-induced germinal centers (GC) and impaired long-term humoral immunity to Bb and unrelated vaccine antigens. IL-10, a potent immunoregulatory cytokine, is strongly induced during Bb infection, limiting Bb tissue clearance. However, the mechanisms by which IL10 acts to limit effective immunity remains unknown. Here we investigated whether blockade of IL10 can improve adaptive immunity to Bb.
Methods: Groups of C57BL/6 mice were treated with anti–IL-10 receptor antibody (αIL-10R) or control rat IgG prior to infection with Bb. Some mice were immunized in addition with influenza virions in alum. Serum antibody responses were measured by ELISA. Flow cytometric analysis assessed GC B and T follicular helper (Tfh) cell populations, and PCR for Bb flaB on various tissues quantified bacterial loads.
Results: On day 30 after infection, αIL-10R–treated mice had increased total and Bb-specific serum IgG, as well as enhanced responses to influenza vaccination. Flow cytometry demonstrated increased GC B and Tfh populations, and qPCR revealed reduced Bb loads compared to control-treated mice. Using IL-10–GFP reporter mice, we identified CD4⁺ T and B cells as predominant sources of IL-10.
Conclusion: Ongoing studies using CD4-Cre and mb1-Cre IL-10flx/flx mice will define the impact of each IL10 cell source on humoral immune responses to Bb and on GC maintenance. These results demonstrate the critical role of Bb-induced IL10 in suppression of effective adaptive immunity to Bb, identifying IL-10 as a potential therapeutic target for improving immunity and Bb clearance in Lyme disease patients.
