Pelvic and Inguinal Lymphadenopathy in a Murine Model of Lyme Disease: Is LD-Gynecological Pathology Immune-Mediated? 2257953

Introduction Lyme disease (LD) has been linked to gynecological complications including endometriosis, and uterine fibroids. Epidemiological data suggest increased incidence of these conditions among previously infected individuals, yet mechanisms remain unclear. We hypothesized that systemic infection induces persistent reproductive tract pathology and local immune activation, measurable through longitudinal imaging. Methods Female mice were intradermally infected with Bb. Weekly in vivo imaging (IVIS and MRI) monitored bacterial burden, uterine morphology, and lymph node changes. Blood, urine, and vaginal fluid were collected at serial timepoints for microbiological and immunological analyses. An AI-based segmentation pipeline quantified tissue structures. Histopathology of the reproductive tract and pelvic lymph nodes characterized structural and immune alterations. Results Infected mice developed uterine cysts and morphological changes by 10 weeks post-infection. IVIS confirmed Bb colonization of the vagina and bladder, while MRI best captured organ abnormalities. Iliacus medialis and inguinal lymph nodes exhibited sustained enlargement beyond 12 weeks. Flow cytometry at 15 weeks revealed pronounced B-cell proliferation without an increase in antibody-secreting or CD4+ T cells. Pelvic lymphadenopathy reflected persistent infection rather than bacterial load. Combined antibiotic treatment fully resolved infection and reversed lymphadenopathy. Conclusion Bb infection induces progressive uterine pathology and chronic pelvic lymphadenopathy, highlighting the link between infection and immune dysregulation in gynecological disease. MRI with AI-driven analysis provides a powerful platform for tracking disease progression. Persistent lymphoid activation occurs independently of bacterial burden but is reversible with combined antibiotic therapy, offering insights into mechanisms and therapeutic targets in LD-associated gynecopathology.