Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs.

Abstract

BACKGROUND: 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. RESULTS: After infection with the HPI/HPIstrains 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-1&#x3b2;, IL-18 and GSDMD, with significantly higher levels detected in the HPIgroup compared to those in the HPIgroup (P&#x2009;<&#xa0;0.01 or P&#x2009;<&#xa0;0.05). HPIstrain is more pathogenic than HPIstrain. CONCLUSION: 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-1&#x3b2; and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.