Effect Of NLRP3 Inflammasome On A Mouse Model Of Staphylococcus Aureus-induced Bloodstream Infection

OBJECTIVEThe NLRP3 inflammasome plays an important role in many inflammatory diseases and may have a similar role in Staphylococcus aureus(S. aureus)-induced bloodstream infections(BSIs). We therefore set up a C57BL/6 mouse model of BSIs induced by S. aureusand explored the role of the NLRP3 inflammasome in this model.METHODSMice were classified as PBS control group and BSIs group (sacrificed 24 hours and 48 hours post-infection respectively).The bacterial counting and cytokines(IL-1βand IL-18) of serum and tissues were measured in both groups.Real-time PCR analysis and western blot analysis were used to detect the NLRP3,ASC,Caspase-1 mRNA and proteins.Histopathologic changes were assessed by Hematoxylin-eosin staining qualitatively andimmunohistochemistry semi-quantitatively.RESULTSColony counting of tissue homogenates(liver,lungs,kidneys)significantly elevated at 24h and 48h post-infection in BSIs group. Hematoxylin-eosin staining showed that tissues in BSIs group had inflammatory cell infiltration and even abscess or necrosis. The damages of the tissues were aggravated gradually over time.Levels of IL-1β and IL-18 in serum and tissue homogenates which were NLRP3 inflammasome-dependent cytokines increased significantly in S.aureus-induced BSIs mice. Real-time PCR showed BSIs significantly increased ASC and caspase-1 mRNA expression in all the three tissues after 48h infection and the expression of NLRP3 mRNA in liver and lungs tissues increased obviously from 24h post-infection. Western blot and immunohistochemistry showed the significant elevation of NLRP3, ASC,pro-casepase-1 and caspase-1 p20 protein levels in S. aureus-induced BSIs.CONCLUSIONSThese results demonstrated that NLRP3 inflammasome activation was associated with the S. aureus-induced BSIs, and the expression level of the NLRP3 inflammasome was correlated with the severity of S. aureus-induced BSIs. It may offer a new direction for studying the underlying mechanisms of bloodstream infections or sepsis and will probably provide a new treatment target for S. aureus-induced BSIs.