{"title":"Severe Inflammation Caused by Coinfection of PCV2 and Glaesserella parasuis Is Associated with Pyroptosis via Noncanonical Inflammasome Pathway","authors":"Jiahui An, Chao Zhang, Jinshuang Cai, Yufeng Li","doi":"10.1155/2022/7227099","DOIUrl":null,"url":null,"abstract":"Coinfections of porcine circovirus type 2 (PCV2) and Glaesserella parasuis (G. parasuis) are widely existing in the swine industry worldwide. However, the mechanisms for this coinfection remain unclear. The aim of this study is to assess whether the coinfection PCV2 and G. parasuis would affect the inflammatory response and related mechanisms. In this study, BALB/c mice and RAW264.7 cells were used to study the inflammation and related mechanism caused by the coinfection of PCV2 and G. parasuis. Coinfection with PCV2 and G. parasuis significantly increased the mortality of mice and led to the development of more severe lung and spleen lesions compared with single agent infection. Especially, coinfection significantly increased the bacterial loads in the lungs. Coinfection with PCV2 and G. parasuis can enhance RAW264.7 cell phagocytosis and elimination to G. parasuis. Cell death rate of cells increased in coinfection was measured with Flow cytometry. Moreover, coinfection led to the downregulation of the expression of TNFα and IL-8 in comparison with G. parasuis infection, but the maturation of interleukin-1β (IL-1β) was significantly upregulated. Our study firstly revealed that coinfection of PCV2 and G. parasuis can increase the phagocytosis of cells to G. parasuis, and LPS in the cytoplasm will induce the maturation of caspase-11 and lead to the cleavage of Gasdermin D (GSDMD) to cause pyroptosis by noncanonical pathway. The revealing of mechanisms associated with coinfection with PCV2 and G. parasuis will provide a scientific basis for investigating the synergistic infection mechanisms between viruses and bacteria.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1155/2022/7227099","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Coinfections of porcine circovirus type 2 (PCV2) and Glaesserella parasuis (G. parasuis) are widely existing in the swine industry worldwide. However, the mechanisms for this coinfection remain unclear. The aim of this study is to assess whether the coinfection PCV2 and G. parasuis would affect the inflammatory response and related mechanisms. In this study, BALB/c mice and RAW264.7 cells were used to study the inflammation and related mechanism caused by the coinfection of PCV2 and G. parasuis. Coinfection with PCV2 and G. parasuis significantly increased the mortality of mice and led to the development of more severe lung and spleen lesions compared with single agent infection. Especially, coinfection significantly increased the bacterial loads in the lungs. Coinfection with PCV2 and G. parasuis can enhance RAW264.7 cell phagocytosis and elimination to G. parasuis. Cell death rate of cells increased in coinfection was measured with Flow cytometry. Moreover, coinfection led to the downregulation of the expression of TNFα and IL-8 in comparison with G. parasuis infection, but the maturation of interleukin-1β (IL-1β) was significantly upregulated. Our study firstly revealed that coinfection of PCV2 and G. parasuis can increase the phagocytosis of cells to G. parasuis, and LPS in the cytoplasm will induce the maturation of caspase-11 and lead to the cleavage of Gasdermin D (GSDMD) to cause pyroptosis by noncanonical pathway. The revealing of mechanisms associated with coinfection with PCV2 and G. parasuis will provide a scientific basis for investigating the synergistic infection mechanisms between viruses and bacteria.
猪圆环病毒2型(PCV2)和副猪格雷瑟菌(G.副猪)的共感染在世界范围内广泛存在。然而,这种合并感染的机制尚不清楚。本研究的目的是评估PCV2和副猪螺旋体共同感染是否会影响炎症反应及其相关机制。本研究采用BALB/c小鼠和RAW264.7细胞,研究PCV2和副猪螺旋体共同感染引起的炎症及相关机制。与单药感染相比,PCV2和副猪G.联合感染可显著提高小鼠死亡率,并导致更严重的肺和脾脏病变。特别是,合并感染显著增加了肺部的细菌负荷。PCV2与副猪螺旋体共感染可增强RAW264.7细胞对副猪螺旋体的吞噬和清除。用流式细胞术检测合并感染增加的细胞死亡率。此外,与副猪螺旋体感染相比,共感染导致TNFα和IL-8的表达下调,但白细胞介素-1β (IL-1β)的成熟水平显著上调。本研究首次发现PCV2与副猪螺旋体共感染可增加细胞对副猪螺旋体的吞噬能力,细胞质中的LPS可诱导caspase-11成熟,导致Gasdermin D (GSDMD)裂解,通过非典型途径引起焦亡。揭示PCV2与副猪弧菌共感染的相关机制,将为进一步研究病毒与细菌的协同感染机制提供科学依据。
期刊介绍:
Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.