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

초록

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 & times; 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.

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