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Maturation and localization of macrophages and microglia during infection with a neurotropic murine coronavirus
Journal article   Open access   Peer reviewed

Maturation and localization of macrophages and microglia during infection with a neurotropic murine coronavirus

Steven P Templeton, Taeg S Kim, Katherine O'Malley and Stanley Perlman
Brain pathology (Zurich, Switzerland), Vol.18(1), pp.40-51
01/2008
DOI: 10.1111/j.1750-3639.2007.00098.x
PMCID: PMC7596182
PMID: 17935605
url
https://doi.org/10.1111/j.1750-3639.2007.00098.xView
Published (Version of record) Open Access

Abstract

Macrophages and microglia are critical in the acute inflammatory response and act as final effector cells of demyelination during chronic infection with the neutrotropic MHV-JHM strain of mouse hepatitis virus (MHV-JHM). Herein, we show that "immature" F4/80(+)Ly-6C(hi) monocytes are the first cells, along with neutrophils, to enter the MHV-JHM-infected central nervous system (CNS). As the infection progresses, macrophages in the CNS down-regulate expression of Ly-6C and CD62L, consistent with maturation, and a higher frequency express CD11c, a marker for dendritic cells (DCs). Microglia also express CD11c during this phase of the infection. CD11c(+) macrophages in the infected CNS exhibit variable properties of immature antigen-presenting cells (APCs), with modestly increased CD40 and MHC expression, and equivalent potent antigen uptake when compared with CD11c(-) macrophages. Furthermore, CDllc(+) and F4/80(+) macrophages and microglia are localized to areas of demyelination, in some instances directly associated with damaged axons. These results suggest that chronic CNS infection results in the appearance of CD11c-expressing macrophages from the blood that exhibit properties of immature APCs, are closely associated with areas of demyelination, and may act as final effectors of myelin destruction.
Humans Brain - virology CD11 Antigens - immunology Macrophages - virology Microglia - immunology Demyelinating Diseases - immunology Microglia - pathology Demyelinating Diseases - pathology Macrophages - immunology Disease Models, Animal Biomarkers - metabolism Demyelinating Diseases - physiopathology Macrophages - pathology Myelin Sheath - immunology Myelin Sheath - pathology Encephalitis - virology Mice, Inbred C57BL Biomarkers - analysis Encephalitis - pathology Encephalitis - immunology Mice, Transgenic Murine hepatitis virus - pathogenicity Coronavirus Infections - immunology Cell Differentiation - immunology Animals Coronavirus Infections - virology Axons - pathology Microglia - virology Coronavirus Infections - pathology Brain - pathology Mice HeLa Cells Axons - immunology Chemotaxis, Leukocyte - immunology Brain - immunology Axons - virology

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