PMID- 16691560
OWN - NLM
STAT- MEDLINE
DCOM- 20060915
LR  - 20071114
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 54
IP  - 2
DP  - 2006 Aug 1
TI  - Altered immune response to CNS viral infection in mice with a conditional 
      knock-down of macrophage-lineage cells.
PG  - 71-80
AB  - 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.
CI  - Copyright 2006 Wiley-Liss, Inc.
FAU - Carmen, Jessica
AU  - Carmen J
AD  - Department of Molecular Microbiology and Immunology, Johns Hopkins University 
      Bloomberg School of Public Health, Baltimore, Maryland, USA.
FAU - Gowing, Genevieve
AU  - Gowing G
FAU - Julien, Jean-Pierre
AU  - Julien JP
FAU - Kerr, Douglas
AU  - Kerr D
LA  - eng
GR  - F31 NS50412-01/NS/NINDS NIH HHS/United States
GR  - R01 NS047192-01A1/NS/NINDS NIH HHS/United States
GR  - R01 NS50412-01/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
SB  - IM
MH  - Alphavirus Infections/genetics/*immunology
MH  - Animals
MH  - Brain/immunology/virology
MH  - Cell Lineage/genetics/immunology
MH  - Central Nervous System Viral Diseases/genetics/*immunology
MH  - Macrophages/*immunology/*virology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Sindbis Virus/genetics/immunology
MH  - Spinal Cord/immunology/virology
EDAT- 2006/05/13 09:00
MHDA- 2006/09/16 09:00
CRDT- 2006/05/13 09:00
PHST- 2006/05/13 09:00 [pubmed]
PHST- 2006/09/16 09:00 [medline]
PHST- 2006/05/13 09:00 [entrez]
AID - 10.1002/glia.20359 [doi]
PST - ppublish
SO  - Glia. 2006 Aug 1;54(2):71-80. doi: 10.1002/glia.20359.