Altered immune response to CNS viral infection in mice with a conditional knock-down of macrophage-lineage cells
Article first published online: 11 MAY 2006
Copyright © 2006 Wiley-Liss, Inc.
Volume 54, Issue 2, pages 71–80, 1 August 2006
How to Cite
Carmen, J., Gowing, G., Julien, J.-P. and Kerr, D. (2006), Altered immune response to CNS viral infection in mice with a conditional knock-down of macrophage-lineage cells. Glia, 54: 71–80. doi: 10.1002/glia.20359
- Issue published online: 26 JUN 2006
- Article first published online: 11 MAY 2006
- Manuscript Accepted: 18 APR 2006
- Manuscript Received: 27 FEB 2006
- SMA. Grant Number: SMA-KER03-06
- NINDS. Grant Numbers: F31 NS34175, R01 NS50412-01, R01 NS047192-01A1
- ALS Association. Grant Number: 639
- Muscular Dystrophy Association. Grant Number: MDA3822
- Packard Center for ALS Research (Johns Hopkins University)
Neuroadapted Sindbis Virus (NSV) is a neuronotropic virus that causes hindlimb paralysis in susceptible mice and rats. The authors and others have demonstrated that though death of infected motor neurons occurs, bystander death of uninfected neurons also occurs and both contribute to the paralysis that ensues following infection. The authors have previously shown that the treatment of NSV-infected mice with minocycline, an inhibitor that has many functions within the central nervous system (CNS), including inhibiting microglial activation, protects mice from paralysis and death. The authors, therefore, proposed that microglial activation may contribute to bystander death of motor neurons following NSV infection. Here, the authors tested the hypothesis using a conditional knock-out of activated macrophage-lineage cells, including endogenous CNS macrophage cells. Surprisingly, ablation of these cells resulted in more rapid death and similar weakness in the hind limbs of NSV-infected animals compared with that of control animals. Several key chemokines including IL-12 and monocyte chemoattractant protein-1 (MCP-1) did not become elevated in these animals, resulting in decreased infiltration of T lymphocytes into the CNS of the knock-down animals. Either because of the decreased macrophage activation directly or because of the reduced immune cell influx, viral replication persisted longer within the nervous system in knock-down mice than in wild type mice. The authors, therefore, conclude that although macrophage-lineage cells in the CNS may contribute to neurodegeneration in certain situations, they also serve a protective role, such as control of viral replication. © 2006 Wiley-Liss, Inc.