Figure 5.

Chemokine-mediated leukocyte recruitment and progression of local inflammation. As a consequence of endothelial activation by pro-inflammatory cytokines, such as TNF, and infected erythrocytes, chemokines are secreted from endothelial cells, which initiate recruitment of leukocytes expressing the respective chemokine receptors, including macrophages, monocytes, neutrophils, and T cell. These cell types were also found to sequester in the microvasculature during human CM as well as murine ECM (Hunt and Grau, 2003; Renia et al., 2012). Upon arrival at the site of the inflammatory insult, these leukocyte subsets may in turn secrete cytokines as well as chemokines, thereby further promoting endothelial activation and leukocyte recruitment. Thus, a feed-forward loop is initiated which exacerbates local inflammation in the brain.