Maturation and localization of macrophages and microglia during infection with a neurotropic murine coronavirus.
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.
Templeton
Steven P
SP
University of Iowa, Iowa City, IA, USA.
Kim
Taeg S
TS
O'Malley
Katherine
K
Perlman
Stanley
S
D000818:Animals; D001369:Axons / Q000276:immunology / Q000473:pathology / Q000821:virology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018845:CD11 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006517:Murine hepatitis virus / Q000472:pathogenicity; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology
D015415:Biomarkers; D018845:CD11 Antigens