Endothelial cell/macrophage cocultures as a model to studyStreptococcus suis-induced inflammatory responses

Abstract

Endothelial cells and macrophages are thought to play a critical role in the inflammatory response that contributes to meningitis. To investigate the interactions between Streptococcus suis and these two cell types, we developed a coculture model composed of brain microvascular endothelial cells and macrophage-like cells, and characterized the production of proinflammatory cytokines, chemokines, prostaglandin E(2) (PGE(2)), and matrix metalloproteinase 9 (MMP-9) following a challenge with bacteria. Streptococcus suis cells stimulated the secretion of all the inflammatory mediators as well as MMP-9 in the coculture model. Responses to S. suis infection were influenced by endothelial cell/macrophage ratios and were dependent on the multiplicity of infection. Except for IL-6, significantly higher amounts of inflammatory mediators and MMP-9 were produced with the coculture model at an endothelial cell/macrophage ratio of 1 : 10 than at a ratio of 1 : 1. When infected with S. suis, endothelial cells and macrophages acted in synergy to increase the secretion of IL-6 and PGE(2). Using a model that more closely reproduces the in vivo situation, we showed that S. suis can induce the secretion of high levels of inflammatory mediators and MMP-9, which may contribute to the development of meningitis.