Inflammatory responses and histopathological changes in a mouse model of Staphylococcus aureus-induced bloodstream infections

Abstract

Introduction: Staphylococcus aureus-induced bloodstream infections (BSIs) remain a prevalent clinical challenge and the underlying pathogenesis is still poorly understood. The aim of this study was to investigate the inflammatory responses and histopathological changes in BSIs in mice. Methodology: Male C57BL/6 mice were inoculated with S. aureus intravenously to induce BSIs. The survival rate, weight loss, and murine sepsis scores (MSS) were monitored in BSI and phosphate-buffered saline (PBS) control mice. Blood samples and tissue homogenates were plated on agar plates to determine the bacterial burden. Inflammatory proteins and cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. Histopathologic changes were assessed by pathological inflammation score (PIS) and macroscopic and microscopic examinations. Results: BSI mice induced by 4.5 × 10 8 CFU/mL S. aureus showed ~70% survival rate, higher sepsis scores, significantly decreased body weight, elevated levels of white blood cell (WBC) counts, C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Prominent correlations were found between elevated CRP and PCT levels as well as among IL-1β, IL-6, and TNF-α. Pathological changes and higher PIS were also observed in BSI mice. Conclusions: Our results demonstrate that inflammatory proteins (PCT and CRP) and cytokines (IL-6, IL-1β and TNF-α) play an important role in the inflammatory responses and histopathological changes in S. aureus-induced BSIs.