Abstract
Regulatory T cells (Tregs) regulate immune responses and maintain host immune homeostasis. Tregs contribute to the disease progression of several chronic infections by oversuppressing immune responses via the secretion of immunosuppressive cytokines, such as transforming growth factor (TGF)-β and interleukin-10. In the present study, we examined the association of Tregs with Mycoplasma bovis infection, in which immunosuppression is frequently observed. Compared with uninfected cattle, the percentage of Tregs, CD4+CD25highFoxp3+ T cells, was increased in M. bovis-infected cattle. Additionally, the plasma of M. bovis-infected cattle contained the high concentrations of TGF-β1, and M. bovis infection induced TGF-β1 production from bovine immune cells in in vitro cultures. Finally, we analyzed the immunosuppressive effects of TGF-β1 on bovine immune cells. Treatment with TGF-β1 significantly decreased the expression of CD69, an activation marker, in T cells, and Th1 cytokine production in vitro. These results suggest that the increase in Tregs and TGF-β1 secretion could be one of the immunosuppressive mechanisms and that lead to increased susceptibility to other infections in terms of exacerbation of disease during M. bovis infection.
Highlights
Bovine mycoplasmosis caused by Mycoplasma bovis is prevalent in many countries, including Japan [1,2,3,4], and is characterized by chronic pneumonia, otitis, arthritis, and therapy-resistant mastitis [5,6,7,8]
A previous study has shown that the transforming growth factor (TGF)-β1 secretion from Tregs reduces antiviral cytokine activities and the cytotoxicity of natural killer (NK) cells in cattle infected with bovine leukemia virus [23]
Flow cytometric analysis revealed that the proportion of forkhead box P3 (Foxp3)+ cells in CD4+CD25high cells was increased in M. bovis-infected cattle (Figures 1A,B, Table 1)
Summary
Bovine mycoplasmosis caused by Mycoplasma bovis is prevalent in many countries, including Japan [1,2,3,4], and is characterized by chronic pneumonia, otitis, arthritis, and therapy-resistant mastitis [5,6,7,8]. The detailed mechanisms underlying the exacerbation of disease by co-infections during bovine mycoplasmosis have not been fully elucidated. Several studies have demonstrated that M. bovis suppresses lymphocyte activities such as Th1 cytokine production and induces lymphocyte apoptosis in vitro [9, 10]. The PD-1/PD-L1 pathway and PGE2 exert suppressive effects on Th1 cytokine production, such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, from bovine immune cells [13, 14]. The inhibition of the PD-1/PD-L1 pathway and PGE2 production in vitro activates M. bovis-specific Th1 responses [11, 12], which suggests that these inhibitory molecules might be involved in the immunosuppression during bovine mycoplasmosis. The detailed mechanisms of the immune suppression in this infection have not been fully elucidated
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