Cytokine gene expression after Staphylococcus aureus infection

Abstract

Staphylococcus aureus (S. aureus) is a virulent pathogen capable of causing sepsis and shock. Little is known about the host response to staphylococcal bacterial infection. To identify the mechanisms involved in S. aureus infection, we analyzed the expression of cytokines in cultured human endothelial cells (EC) and monocytes after infection with S. aureus. An animal model was also established to study pathologic changes and cytokine induction after S. aureus infection in vivo.;Infection of EC with the Wb isolate of S. aureus resulted in the induction of IL-1{dollar}\beta{dollar} and IL-6. The laboratory isolate 8325-4 did not induce cytokine expression and was internalized by EC much less than Wb. Cytochalasin D, an inhibitor of endocytosis, prevented cytokine induction in EC after S. aureus infection, indicating that internalization of S. aureus by EC is necessary for cytokine expression.;Inhibition of internalization of the bacteria did not affect cytokine induction in monocytes. Live 8325-4, heat-killed-Wb (HK-Wb) or Wb cell wall components treatment induced IL-1{dollar}\beta{dollar} expression in monocytes, but not in EC, suggesting that induction of cytokine gene expression in S. aureus-infected EC and monocytes is through a different mechanism.;Induction of IL-8 and E-selectin in EC was detected after infection with S. aureus. Transendothelial migration of human neutrophils occurred in the presence of supernatants from S. aureus-infected EC, demonstrating that EC and EC-derived IL-8 may play an important role in recruitment of leukocytes during S. aureus infection.;The supernatant from a bacterial culture of 8325-4 inhibited internalization of Wb by EC and induction of cytokine gene expression in Wb-infected EC. Partial characterization of the inhibitor demonstrated that the factor is greater than 10 kDa and contains both lipid and protein.;A mouse model was established to study pathologic changes and cytokine gene expression in sera and tissues and after S. aureus infection. Tissue inflammation and progressive damage appeared to correlate with elevated levels of TNF, IL-1 and IL-6 in the infected animals. The results provide a baseline for subsequent studies on the role of inflammatory cytokines in the pathogenesis of staphylococcal diseases including sepsis.