Chemokines Referee Inflammation within the Central Nervous System during Infection and Disease

Figure 2

Neuroprotective roles of chemokines in response to viral infection of the CNS. Functional roles of chemokines in attracting and activating lymphocytes into the CNS during acute viral infection. Monocytes are attracted into the CNS via the chemokine CCL5 and its receptor CCR5. Macrophages produce IL-1β within the CNS and ensure full activation and CXCL12-mediated interactions of infiltrating leukocytes. CXCR4-expressing lymphocytes are captured by endothelial expression of CXCL12 within the perivascular spaces, which promotes CD4⁺ T-cell help to infiltrate CD8⁺ T lymphocytes. In addition to full activation, lymphocyte egress from perivascular spaces requires CD40. During the acute stage of disease, virally infected neurons secrete CXCL10 and CCL5 that attract activated T lymphocytes bearing the receptor CXCR3 and/or CCR5 into the parenchyma. CD8⁺ and CD4⁺ T lymphocytes mediate viral control through direct cytolytic activity and/or cytokine secretion.