College of Animal Science and Technology, Yunnan Agricultural University, Kunming, 650201, China.
College of Veterinary Medicine, Yunnan Agricultural University, Kunming, 650201, China.
BMC Vet Res. 2021 Mar 7;17(1):114. doi: 10.1186/s12917-021-02824-x.
Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study.
After infection with the HPI/HPI strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate dehydrogenase (LDH) assay. HPI/HPI-infection was accompanied by upregulated expression levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD, with significantly higher levels detected in the HPI group compared to those in the HPI group (P < 0.01 or P < 0.05). HPI strain is more pathogenic than HPI strain.
Our findings indicate that pathogenic E. coli HPI infection of Saba pigs causes pyroptosis of macrophages characterized by upregulated expression of pyroptosis key factors in the NLRP3/ASC/caspase-1 signaling pathway, direct cell membrane pore formation, and secretion of the inflammatory factor IL-1β and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.
细胞焦亡在许多炎症性疾病的发病机制中起着关键作用。本研究将评估致病性大肠杆菌高致病性岛（HPI）感染后巨噬细胞中细胞焦亡的诱导分子机制。
用碘化丙啶（PI）染色和乳酸脱氢酶（LDH）检测法检测到，感染 HPI/HPI 株和 LPS 后，巨噬细胞膜通透性和完整性降低。HPI/HPI 感染伴随着 NLRP3、ASC、半胱天冬酶-1、IL-1β、IL-18 和 GSDMD 的表达水平上调，与 HPI 组相比，HPI 组的表达水平显著更高（P<0.01 或 P<0.05）。HPI 菌株比 HPI 菌株具有更强的致病性。
我们的研究结果表明，致病性大肠杆菌 HPI 感染 Saba 猪引起巨噬细胞焦亡，其特征是 NLRP3/ASC/caspase-1 信号通路中焦亡关键因子的表达上调，直接导致细胞膜孔形成，并激活 NLRP3 和 caspase-1 后下游炎性因子 IL-1β 和 IL-18 的分泌，从而增强炎症反应。
