The Role of T Cells in Toxoplasma gondii-Induced Prostatic Hyperplasia

Abstract

Chronic inflammation is the most common histological feature in Benign Prostatic Hyperplasia (BPH), and T cells are a key component of immune infiltrate. Advanced BPH is commonly associated with the formation of nodules, but it remains unclear whether a link exists among T cell infiltration, nodular development, and BPH progression. Using a Toxoplasma gondii (T. gondii) model and human specimens, we characterize the subtypes of T cells present during prostatic hyperplasia and their association with nodular development of the prostate. Using flow cytometry, we found that infecting male mice with T. gondii resulted in an increase of both CD4+ and CD8+ T cells in the prostate that was most prominent at 14 days post-infection. Next, we established the presence of microglandular hyperplasia (MGH) and glandular nodule formation at this timepoint through hematoxylin and eosin (H&E) staining. Immunofluorescence revealed that CD8+ cells were found proximal to forming glandular nodules relative to non-nodular glands. We also found that more CD8+ cells localized to non-nodular glands in nodular BPH tissue versus non-nodular BPH tissue. Finally, we discovered a higher prevalence of CD8+ cells in T. gondii IgG+ patients than in IgG- patients. All T. gondii IgG+ patients exhibited nodular BPH, whereas all but one IgG- patient exhibited non-nodular BPH. This study is the first to identify the subsets of T cells in T. gondii-infected mouse prostates. Additionally, the locality of CD4+ and CD8+ T cells to nodular and non-nodular glands within our mouse model and human BPH prostate tissue has never been analyzed. Translationally, CD8+ T cells may enhance nodular BPH progression, and T. gondii infection may promote this CD8+ T cell-mediated response. Future work will focus on dissecting the molecular pathways induced by secreted factors from these CD8+ T cells that may contribute to epithelial cell proliferation and re-activation of glandular patterning in BPH.