The role of chemokines during viral infection of the CNS - PubMed (original) (raw)

Figure 1. Functional roles of chemokines in response to viral infection of the CNS.

Potential roles of chemokines in attracting innate immune cells (A) and lymphocytes (B) into the CNS during acute viral infection. The cartoons emphasize several key points derived from recent studies focusing on experimental infection with neurotropic viruses. (A) Early (days 1–3) after viral infection, activated and/or virally infected astrocytes, microglia, and endothelial cells secrete chemokines that serve to attract myeloid cells to the CNS. Among the earliest cells to respond to viral infection, neutrophils are recruited into the CNS by virtue of CXCR2 responding to ligands expressed within the CNS (e.g., CXCL1). Monocytes are also attracted into the CNS via the chemokine CCL5 and its receptor CCR5. Neutrophils and monocytes participate in the degradation of the blood–brain barrier (BBB), in part through the release of the matrix metalloproteinase MMP-9, and therefore ensure successive infiltration of virus-specific lymphocytes into the CNS. (B) During the acute stage of disease, astrocytes, microglia, neurons, and endothelial cells continue to secrete chemokines, serving to attract activated T lymphocytes, NK cells, and monocytes into the CNS. CD8+ and CD4+ T lymphocytes bearing the receptor CXCR3 and/or CCR5 are attracted by the chemokines CXCL10 and CCL5, respectively, and mediate viral control through direct cytolytic activity and/or cytokine secretion. CXCL12, which signals through CXCR4, may, however, sequester T lymphocytes within the perivascular space and regulate penetration of the parenchyma, thus inhibiting efficient viral clearance.