Porcine circovirus type 2 (PCV-2) and Streptococcus suis (S. suis) are common pathogens in pigs. Both pathogens are associated with the porcine respiratory disease complex. Clinically, coinfection of PCV-2 and S. suis are often detected in pigs with respiratory symptoms, while interactions between the two pathogens during coinfection and the coinfection pathogenesis are poorly understood. In this study, a piglet model coinfected with PCV-2 and Streptococcus suis serotype 2 (SS2) was established; coinfection of piglets increased the contents of SS2 in blood, and piglets showed more severe pneumonia, myocarditis and arthritis. Peripheral blood mononuclear cells (PBMCs) were collected and coinfected piglets showed high expression levels of inflammatory cytokines and TLR2, TLR4, while levels of CD4, CD8 and MHC II were reduced. In addition, in order to further explore the mechanisms of coinfection induced cytokine overexpression, an in vitro model of coinfection with PCV-2 and SS2 was established using cells of the porcine monocytic line 3D4/21. Similar to the in vivo results,coinfected cells exhibited increased expression of the cytokines IL-6, IL-8, TNF-α and the receptors TLR2, TLR4, while they showed a lower expression of MHC II than cells infected with SS2 alone. Furthermore, in coinfected 3D4/21 cells, both MAPK and NF-κB signaling pathways were activated, and the increased expression of IL-8 was related to TLR4. In general, coinfection with PCV-2 and SS2 exacerbated the inflammatory response and probably impaired macrophage antigen presentation, resulting in immune dysregulation and increasing the severity of host infection.

猪圆环病毒2型（PCV-2）和猪链球菌（S. suis）是猪的常见病原体。两种病原体都与猪呼吸系统疾病相关。在临床上，通常在具有呼吸道症状的猪中检测到PCV-2和猪链球菌的共感染，而对共感染过程中两种病原体之间的相互作用以及共感染的发病机理知之甚少。在这项研究中，仔猪模型感染了PCV-2和猪链球菌血清型2（SS2）已建立；仔猪的共感染增加了血液中SS2的含量，仔猪表现出更严重的肺炎，心肌炎和关节炎。收集外周血单个核细胞（PBMC），并发感染的仔猪显示高表达水平的炎症细胞因子和TLR2，TLR4，而CD4，CD8和MHC II的水平则降低。另外，为了进一步探索共感染诱导的细胞因子过表达的机制，使用猪单核细胞系3D4 / 21的细胞建立了PCV-2和SS2共感染的体外模型。类似于体内结果，合并感染的细胞表现出细胞因子IL-6，IL-8，TNF-α和受体TLR2，TLR4的表达增加，而它们的MHC II表达则比单独感染SS2的细胞低。此外，在合并感染的3D4 / 21细胞中，MAPK和NF-κB信号通路均被激活，并且IL-8的表达增加与TLR4有关。通常，与PCV-2和SS2共感染会加剧炎症反应，并可能损害巨噬细胞抗原的呈递，从而导致免疫失调并增加宿主感染的严重性。