Effect of deletion of SUMOylation on dendritic cell function in septic mice and its role in sepsis.

Abstract

To investigate the effect of deletion of small ubiquitin-like modifier (SUMO) on the function of dendritic cells (DC) in septic mice and its role in sepsis. Septic models of DC-specific ubiquitin-conjugating enzyme 9 (UBC9) deficient (UBC9ΔDC) mice and wild type (WT) mice with cecal ligation and puncture (CLP) were established. The differences in 7-day mortality of the mice were analyzed. Bacteria loads of blood, liver, and spleen were tested. ELISA was used to detect the levels of IL-1β, IL-6, IL-18, and TNF-α in plasma and culture medium of bone marrow-derived dendritic cells (BMDC). The levels of cytokine IFN-γ and IL-4 in supernatant of spleen mononuclear cells were detected by ELISA.The expressions of MHC II, CD54, and CD80 on the cell surface of DC were analyzed by flow cytometry. The percentages of Th1, and Th2 cells in spleen mononuclear cells were analyzed by flow cytometry. Compared with the WT septic mice, the 7-day mortality of UBC9ΔDC septic mice was higher (P<0.05). Bacterial loads in blood (P<0.01), liver (P<0.01), and spleen (P<0.05) were significantly increased in UBC9ΔDC septic mice. Levels of IL-1β and IL-18 in plasma and culture supernatant of BMDC were also significantly increased in UBC9ΔDC septic mice (all P<0.01). There was no significant difference in the number of DC and the expression of cell surface molecules in DC of UBC9ΔDC septic mice (all P>0.05).The percentage of Th2 cells was significantly increased in UBC9ΔDC septic mice (P<0.05). The ratio of Th1 to Th2 was decreased in UBC9ΔDC septic mice but the difference was not significant (P>0.05). Levels of IFN-γ and IL-4 were increased in UBC9ΔDC septic mice, and the ratio of IFN-γ to IL-4 were significantly decreased in UBC9ΔDC septic mice (all P<0.05). Deletion of SUMOylation may increase the mortality of mice with sepsis through regulating the release of inflammatory factors from DC and abnormal activation of T cells by DC.