Abstract
Sepsis is associated with bacterial invasion and inflammation and has a high mortality rate. Previous studies have demonstrated that tripartite motif 59 (TRIM59) was involved in NF-κB signaling and could promote phagocytosis of macrophages, but the role of TRIM59 in sepsis is still unknown. In our study, we found that TRIM59 was downregulated in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs). In the cecal ligation and puncture (CLP) sepsis mice model, the mortality of Trim59flox/floxLyz-Cre (Trim59-cKO) mice was higher, the immune cell infiltration and damage of liver and lung were more severe, and bacteria burden was increased. We also found that TRIM59 altered the production of pro-inflammation cytokines, as well as macrophage phagocytosis ability. Further analysis indicated that NF-κB signal pathway and Fcγ receptors might be involved in these regulations. Our study demonstrated for the first time that TRIM59 protects mice from sepsis by regulating inflammation and phagocytosis in macrophages.
Highlights
Sepsis is a life-threatening syndrome that affects the health of millions of patients, especially hospitalized patients
We found that the expression of tripartite motif 59 (TRIM59) was significantly downregulated in LPS-stimulated bone marrow-derived macrophages (BMDMs), and mortality, liver and lung damage, and inflammatory cytokines were increased in Trim59-cKO mice after cecal ligation and puncture (CLP) surgery
Phagocytosis plays an important role in bacteria invasion, so we hypothesized that TRIM59 could affect sepsis by regulating macrophage phagocytosis
Summary
Sepsis is a life-threatening syndrome that affects the health of millions of patients, especially hospitalized patients. The mortality rate of sepsis is as high as 25% [2]. Sepsis certainly imposes significant global health costs due to its high incidence and mortality rates. Macrophages have multiple functions, including: [1] production of inflammatory cytokines, like interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α); [2] phagocytosis of pathogens; and [3] presentation of antigens with major histocompatibility complex (MHC) molecules, cluster of differentiation (CD) 80 and CD86 [3]. TNF, IL-1β, and IL-6 are important cytokines that mediate initial response of innate immune system to infections. TNF and IL-1β both activate endothelial cells and attract circulating polymorphonuclear white blood cells (PMNs) to the infection site. These cytokines enter the bloodstream and cause fever and other systemic symptoms. IL-6 stimulates liver production of acute phase reactants to stimulate the inflammatory response, and stimulates the transformation of bone marrow cells to produce more
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