[LAMTOR2 deficiency exacerbates Klebsiella pneumoniae-induced liver sepsis in mice]

Abstract

Objective To explore the biological function and mechanisms of LAMTOR2 during Klebsiella pneumoniae(K. pneumoniae) induced liver sepsis by establishing late endosomal/lysosomal adaptor 2(LAMTOR2) gene liver conditional knockout mouse model infected by K. pneumoniae. Methods LAMTOR2 gene liver conditional knockout mice (LAMTOR2^flox/flox; Alb-Cre⁺) and littermate controls (LAMTOR2^flox/flox) were generated and bred. LAMTOR2 gene knockout efficiency in liver was determined by real-time quantitative PCR (RT-qPCR) and Western blot analysis. Then, both group mice were infected with K. pneumoniae, and survival rates and liver pathological changes were determined. The expression levels of liver TNF-α, IL-1β and CXCL1 mRNA were detected by RT-qPCR. Results LAMTOR2 gene liver conditional knockout mice were generated and bred successfully; compared to the littermate controls, LAMTOR2^flox/flox, Alb-Cre⁺ mice showed lower survival rates and more severe liver injury. The expression levels of TNF-α, IL-1β and CXCL1 mRNA were reduced in LAMTOR2^flox/flox and the ability of immune response was decreased in mice. Alb-Cre⁺ mice liver compared to these of littermate controls post K. pneumoniae infections. Conclusion LAMTOR2 plays a protective role during K. pneumoniae-induced liver sepsis.