SIGIRR调控PCV2感染猪肺泡巨噬细胞炎性细胞因子表达的机制研究

Porcine circovirus type 2 (PCV2) is the most important vial pathogen for the global swine industry today, which can cause the secretion disorder of inflammatory cytokines and result in immune suppression. Single immunoglobin interleukin-1 receptor related protein (SIGIRR) is a key regulator of TIR signal pathway, which regulates the inflammatory injury and innate immunity by inhibiting the secretion of inflammatory cytokines. Our research found that it was up-regulation of inflammatory cytokines and down-regulation of SIGIRR rapidly when porcine alveolar macrophages (PAM) inoculated with PCV2, which indicated the overexpression of inflammatory cytokines is closely associated with SIGIRR. In this project, the way of differential expression of SIGIRR in PAM induced by PCV2 will be studied by using immunology and molecular biology techniques. Meanwhile, the effect of SIGIRR on the expression of inflammatory cytokines and the leukocytes chemotactic effect of PCV2-infected PAM will be verified by the silence and overexpression of SIGIRR in PAM. In addition, the regulatory mechanisms of SIGIRR on the expression of these cytokines will be elucidated by exploring the key factor of TIR signaling pathway interacted with SIGIRR. The research will be helpful to clarify the mechanisms of immune suppression induced by PCV2.

猪圆环病毒2型（PCV2）是危害养猪业的重要病原，其感染可引起炎性细胞因子分泌紊乱并导致机体免疫抑制。单免疫球蛋白白介素1受体相关蛋白（SIGIRR）是TIR信号通路的关键性调节因子，能抑制炎性细胞因子分泌并调节天然免疫和组织炎性反应。我们前期研究发现PCV2感染猪肺泡巨噬细胞(PAM)后迅速引起SIGIRR下调并伴有炎性细胞因子上调，提示PCV2引起炎性细胞因子过表达可能与SIGIRR有关。本项目利用免疫学和分子生物学技术，进一步研究PCV2感染PAM后诱导SIGIRR差异表达的方式；并通过在PAM内沉默和过表达SIGIRR，验证其对PCV2感染的PAM表达炎性细胞因子和趋化炎性细胞效应的影响；同时探索与SIGIRR相互作用的TIR通路关键因子，阐明SIGIRR在PCV2感染PAM诱导炎性细胞因子表达过程中的调控机制，为深入解析PCV2引起机体免疫抑制的机理提供理论支持。

猪圆环病毒2型（PCV2）是危害养猪业的重要病原，其感染可引起细胞因子分泌紊乱并导致多系统性炎症反应和机体免疫抑制。PCV2感染猪肺泡巨噬细胞(PAM)能引起TIR信号通路的关键性调节因子，单免疫球蛋白白介素1受体相关蛋白（SIGIRR）的下调并伴有炎性细胞因子的上调，提示PCV2引起炎性细胞因子过表达可能与SIGIRR有关。本项目通过对SIGIRR的沉默和过表达，来探索其与PCV2诱导的炎性细胞因子IL-1β差异表达的关联及其调控机制。研究发现在过表达SIGIRR或抑制核转录因子NF-κB活化的情况下，IL-1β表达明显减少，表明PCV2诱导IL-1β上调表达与SIGIRR的下调和NF-κB活化相关。而在SIGIRR敲除的PAM细胞出现IL-1β上调并伴随着NF-κB过度活化，表明SIGIRR能通过抑制NF-κB活化来实现对IL-1β的负调控。对PCV2感染引起SIGIRR下调途径研究发现，ORF3转染及TNF-α处理的PAM内SIGIRR出现下调表达，表明SIGIRR的下调可能与ORF3以及PAM产生的TNF-α的自身调控有关。本研究为临床上PCV2影响猪的多系统炎症发生丰富理论依据。