MOE Joint International Reasearch Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
MOE Joint International Reasearch Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China.
Vet Microbiol. 2020 Apr;243:108653. doi: 10.1016/j.vetmic.2020.108653. Epub 2020 Mar 19.
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。这两种病原体都与猪呼吸道疾病综合征有关。临床上，在有呼吸道症状的猪中经常检测到 PCV-2 和 S. suis 的混合感染，而在混合感染过程中两种病原体之间的相互作用以及混合感染的发病机制尚不清楚。在本研究中，建立了猪圆环病毒 2 型和猪链球菌血清型 2（SS2）混合感染的仔猪模型；仔猪混合感染增加了血液中 SS2 的含量，仔猪表现出更严重的肺炎、心肌炎和关节炎。采集外周血单核细胞（PBMC），发现混合感染仔猪的炎症细胞因子和 TLR2、TLR4 表达水平升高，而 CD4、CD8 和 MHC II 表达水平降低。此外，为了进一步探讨混合感染诱导细胞因子过度表达的机制，建立了 PCV-2 和 SS2 混合感染猪单核细胞系 3D4/21 细胞的体外模型。与体内结果相似，感染细胞中细胞因子 IL-6、IL-8、TNF-α 和受体 TLR2、TLR4 的表达增加，而与单独感染 SS2 的细胞相比，MHC II 的表达降低。此外，在混合感染的 3D4/21 细胞中，MAPK 和 NF-κB 信号通路均被激活，IL-8 的表达增加与 TLR4 有关。总的来说，PCV-2 和 SS2 的混合感染加重了炎症反应，并可能损害巨噬细胞的抗原呈递，导致免疫失调，增加宿主感染的严重程度。
