MLKL-mediated regulation against Staphylococcus aureus infection-induced liver and kidney damage in mice
In this study,we analyzed the secretion of pro-inflammatory cytokines(TNF-α and IL-1β)and anti-inflammatory cytokine(IL-10),as well as the level of tissue organ damage,recruit-ment of neutrophils in blood of S.aureus-infected MLKL knockout(MLKL-/-)and C57BL/6J mice by ELISA,immunofluorescence,hematoxylin-eosin staining and flow cytometry,respectively.The results showed that the levels of TNF-α secretion were significantly higher in the liver and kidneys of S.aureus-infected MLKL-/-mice compared to C57BL/6J mice(P＜0.001).Moreover,the secretion level of IL-10 in the liver and kidneys of S.aureus-infected C57BL/6J mice was sig-nificantly higher than in MLKL-/-mice(P＜0.05).Immunofluorescence staining revealed that the expression of the tissue damage marker HMGB1 protein in the liver and kidneys was higher in S.aureus-infected MLKL-/-mice compared to C57BL/6J mice(P＜0.01).Histopathological analy-sis showed that the extent of liver and kidney damage in S.aureus-infected MLKL-/-mice was significantly higher than in C57BL/6J mice.After S.aureus infection,the proportion of CD11b and Gr-1 double positive cells in the blood of MLKL-/-mice was significantly higher than in C57BL/6J mice(P＜0.01).The mice infected with different doses of S.aureus,MLKL-mice had a lower survival rate compared to C57BL/6J mice.These results indicate that MLKL has a certain down-regulatory effect on host cytokine secretion induced by S.aureus infection,thereby exerting a pro-tective role in host organ damage and reducing mouse mortality.
NETL
NSTL
万方数据
