Shujie Wang, Chuang Lyu, Guixin Duan, Fandan Meng, Yongbo Yang, Ying Yu, Xijun He, Zhenzhong Wang, Marcelo Gottschalk, Ganwu Li, Xuehui Cai, Gang Wang.

Infect Immun. 2020 Jan 13. pii: IAI.00950-19. doi: 10.1128/IAI.00950-19

Abstract

Streptococcus suis serotype 2 is an important bacterial pathogen of swine and also an emerging zoonotic agent that may be harmful to human health. Although the virulence genes of S. suis 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 S. suis on specific populations of thymic and immune cells in infected mice. Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling (TUNEL) assays revealed that S. suis infection induced apoptosis in CD3+, CD14+ and epithelial cells from the thymus. S. suis infection resulted in a rapid depletion of mitochondrial permeability and release of cytochrome c (CytC) and apoptosis-inducing factor (AIF) through up-regulation of Bax and down-regulation of Bcl-xl and Bcl2 expression in thymocytes. Moreover, S. suis infection increased cleavage of caspase-3, -8, -9. Thus, S. suis 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 pro-inflammatory cytokines in the serum including interleukin (IL)-2, IL-6, IL-12 (p70), tumor necrosis factor (TNF), and IL-10 was observed in mice after S. suis type 2 infection. Taken together, these results suggest that S. suisinfection can cause atrophy of the thymus and induces apoptosis of thymocytes in mice, thus likely suppressing host immunity.

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