Mechanism of inflammatory responses and histopathological changes in Staphylococcus aureus induced bloodstream infections in mice / 中国免疫学杂志

ABSTRACT

Objective:To establish mice models of Staphylococcus aureus bloodstream infections so as to investigate the inflammatory responses and histopathological changes in bloodstream infections (BSIs) mice.Methods:C57BL/6 mice were inoculated with S.aureus intravenously or intraperitoneally to induce BSIs.Survival rate , weight loss and murine sepsis scores ( MSS ) were ob-served.Blood samples and tissue homogenates were plated on agar to determine bacterial burden .Inflammatory proteins ( CRP,PCT) and cytokines ( IL-1β, IL-6 and TNF-α) were determined by ELISA kits.Histopathologic changes were also assessed by pathological inflammation scores(PIS),macroscopic and microscopic examination.Results: About 70% survival rate was observed in 4.5×108 CFU/ml S.aureus induced BSIs mice.Body weight decreased and sepsis scores increased significantly since 24 h post-infection in BSIs mice,and more prominent in IV group.The counts of WBC began to significantly increase at 3 h post-infection,while CRP and PCT levels peaked at 48 hours in IV and IP groups ( 60.80 ±5.63 vs 40.58 ±7.54 for CRP;6.796 ±1.16 vs 2.740 ±0.36 for PCT ) . Moreover,the levels of IL-1β,IL-6 and TNF-αin serum and tissue homogenates ( liver,lungs,and kidneys ) were significantly elevated in BSIs mice.Pathological changes in tissues (liver,lungs and kidneys) and higher pathological inflammation scores (PIS) were also observed in BSIs mice.Conclusion:Our study represents an effective approach for S.aureus BSIs model to mimic human sepsis.Our results demonstrated that inflammation protein (PCT,CRP) and cytokines(IL-6,IL-1βand TNF-α) play an important role in the in-flammatory response and histopathological changes during BSIs caused by S .aureus.