Streptococcus suis Serotype 2 Infection Causes Host Immunomodulation through Induction of Thymic Atrophy.

serotype 2 is an important bacterial pathogen of swine and is also an emerging zoonotic agent that may be harmful to human health. Although the virulence genes of have been extensively studied, the mechanisms by which they damage the central immune organs have rarely been studied. In the current work, we wanted to uncover more details about the impact and mechanisms of on specific populations of thymic and immune cells in infected mice. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assays revealed that infection induced apoptosis in CD3, CD14, and epithelial cells from the thymus. infection resulted in a rapid depletion of mitochondrial permeability and release of cytochrome (CytC) and apoptosis-inducing factor (AIF) through upregulation of Bax expression and downregulation of Bcl-xl and Bcl2 expression in thymocytes. Moreover, infection increased cleavage of caspase-3, caspase-8, and caspase-9. Thus, induced thymocyte apoptosis through a p53- and caspase-dependent pathway, which led to a decrease of CD3 cells in the thymus, subsequently decreasing the numbers of CD4 and CD8 cells in the peripheral blood. Finally, expression dysregulation of proinflammatory cytokines in the serum, including interleukin 2 (IL-2), IL-6, IL-12 (p70), tumor necrosis factor (TNF), and IL-10, was observed in mice after type 2 infection. Taken together, these results suggest that infection can cause atrophy of the thymus and induce apoptosis of thymocytes in mice, thus likely suppressing host immunity.