Altered splenic T-cell subpopulation dynamics in a murine model of bovine digital dermatitis-associated Treponema...

Bovine digital dermatitis (BDD) is an infectious hoof disease associated with multiple Treponema species, causing significant economic and welfare concerns in the cattle industry. Studies regarding T-cell mediated immune responses are limited in BDD. Using a mouse model, this study analyzed different T-cell subsets involved in immune responses against BDD-associated treponemes. Additionally, this study measured Treponema-specific IgG antibody titers to elucidate humoral immune responses. Mice were experimentally infected with 2 × 10⁹ cells/mL of live T. phagedenis HNW1, T. pedis GNW45, T. pedicariei and their combination. After 1, 3, and 6 weeks, mice were sacrificed, blood serum was collected and T-cells were isolated from the spleen. Treponema-specific IgG antibody titers were measured using enzyme-linked immunosorbent assay (ELISA) and T-cell phenotypes were analyzed using flow cytometry. All Treponema-infected groups recorded a high Treponema-specific IgG antibody titers from 1 week to 6 weeks post-infection. A reduction in subpopulation percentage of CD44⁺ expressing T-cell on both CD4⁺ and CD8⁺ were observed in Treponema-infected groups from 1 week to 6 weeks post-infection suggesting a decrease in T-cell activation. Higher subpopulation percentage of CD44⁺, CD62L⁺ expressing T-cells on both CD4⁺ and CD8⁺ were observed in Treponema-infected groups at 1 week post-infection which might indicate a reduction in the activity effector T-cells, thereby decreasing their effector functions against Treponema infection. Higher subpopulation percentage of CD8⁺, CD44⁺ T-cells expressing IRF4⁺ and CD27⁺ without CD127 expression were observed in all Treponema-infected groups from 1 week to 6 weeks post-infection. These findings may be associated with altered cytotoxic T-cell differentiation and exhaustion-like T-cell features. The significantly higher subpopulation percentage of CD4⁺ T-cells expressing Foxp3⁺ compared to other CD4⁺ helper T-cell subsets suggests that Treponema spp. infection may be associated with a regulatory T-cell-related immune response. Our findings reveal that BDD-associated Treponema spp. has the potential to impair key aspects of T-cell mediated immunity as indicated by alterations in subpopulation percentage of different T-cell subsets. Collectively, our result advances our understanding of the immunological interactions between BDD-associated treponemes and the host offering valuable insights into the immunopathogenesis of BDD.