| First Author | Getts DR | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 10 | Pages | 2319-37 |
| PubMed ID | 18779347 | Mgi Jnum | J:141277 |
| Mgi Id | MGI:3817842 | Doi | 10.1084/jem.20080421 |
| Citation | Getts DR, et al. (2008) Ly6c+ 'inflammatory monocytes' are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis. J Exp Med 205(10):2319-37 |
| abstractText | In a lethal West Nile virus (WNV) model, central nervous system infection triggered a threefold increase in CD45(int)/CD11b(+)/CD11c(-) microglia at days 6-7 postinfection (p.i.). Few microglia were proliferating, suggesting that the increased numbers were derived from a migratory precursor cell. Depletion of 'circulating' (Gr1(-)(Ly6C(lo))CX3CR1(+)) and 'inflammatory' (Gr1(hi)/Ly6C(hi)/CCR2(+)) classical monocytes during infection abrogated the increase in microglia. C57BL/6 chimeras reconstituted with cFMS-enhanced green fluorescent protein (EGFP) bone marrow (BM) showed large numbers of peripherally derived (GFP(+)) microglia expressing GR1(+)(Ly6C(+)) at day 7 p.i., suggesting that the inflammatory monocyte is a microglial precursor. This was confirmed by adoptive transfer of labeled BM (Ly6C(hi)/CD115(+)) or circulating inflammatory monocytes that trafficked to the WNV-infected brain and expressed a microglial phenotype. CCL2 is a chemokine that is highly expressed during WNV infection and important in inflammatory monocyte trafficking. Neutralization of CCL2 not only reduced the number of GFP(+) microglia in the brain during WNV infection but prolonged the life of infected animals. Therefore, CCL2-dependent inflammatory monocyte migration is critical for increases in microglia during WNV infection and may also play a pathogenic role during WNV encephalitis. |
