炎症小体信号通路介导Mo感染性炎症和细胞焦亡的分子机制研究

绵羊肺炎支原体（Mo）引起的羊支原体肺炎是严重危害养羊产业的疾病，感染羊呈现肺组织炎性损伤为特征的单核-巨噬细胞浸润和组织细胞死亡，其机制不明。近年报道，TLRs、NLRs能识别病原相关分子模式，并通过信号传导诱导炎症反应和细胞死亡，参与调控机体清除病原及感染过程，介导细胞凋亡、焦亡等免疫病理过程。团队前期研究也发现TLRs参与Mo引起的炎症性致病过程，且Mo能侵染肺泡巨噬细胞并诱导细胞死亡。据此提出炎症小体信号通路介导Mo感染性炎症反应和细胞焦亡并促进炎症的推论。选择小鼠肺泡巨噬细胞和羊肺泡巨噬细胞为研究对象，明确Mo感染激活肺泡巨噬细胞经TLR2/TLR4或NLRP3经典炎症小体或非经典炎症小体通路表达IL-1β、IL-18等炎性细胞因子和诱导细胞焦亡的分子机制，解释TLRs、NLRs调控细胞炎症反应与疾病发生相关关系，为解析羊支原体肺炎致病机理奠定基础，为该病防治提供新思路。

Mycoplasma pneumonia caused by Mycoplasma pneumoniae (Mo) was a serious disease that endangered the sheep industry. Infected sheep often showed inflammatory injury of lung tissue with monocyte-macrophage infiltration and tissue cell death. Its mechanism was unknown. In recent years, it had been reported that TLRs and NLRs could recognize pathogen-related molecular patterns, induce inflammation and cell death through signal transduction, participate in the regulation of pathogen clearance and infection process, and mediate apoptosis, pyroptosis and other immunopathological processes. Our previous studies had also found that TLRs were involved in the pathogenesis of Mo that could infect alveolar macrophage and induce cell death. Therefore, the molecular mechanism of inflammatory corpuscles and their signaling pathways mediating inflammatory response and cell pyroptosis of Mo was proposed. Mouse alveolar macrophages and sheep alveolar macrophages were selected as the research objects. Western blot, gene silencing and flow cytometry were used to determine the expression of inflammatory cytokines such as IL-1beta and IL-18 and the molecular mechanism of inducing cell death through TLR2/TLR4 or NLRP3 classical inflammatory or non-classical inflammatory pathways. The results will explain the correlation between TLRs and NLRs in regulating cellular inflammatory response and disease. The research will lay the theoretical foundation for the analytical pathogenic mechanism of goats Mycoplasma pneumonia and a new way for disease prevention.