Abstract
Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11b+F4/80+CD11c+MHCIIhighDC-SIGNhighLy6c+ and express high levels of CCR5, CXCL9 and CXCL10 (CCR5+CXCL9/10+ MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route. After differentiation in the spleen, CCR5+CXCL9/10+ MO-DCs traffic to the brain in a CCR2-independent, CCR5-dependent manner, where they amplify the influx of CD8+ T lymphocytes, leading to a lethal neuropathological syndrome.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigens, Protozoan / immunology
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Brain / cytology
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Brain / immunology*
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Brain / pathology
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CD8-Positive T-Lymphocytes / immunology*
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Cell Differentiation / immunology
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Chemokine CXCL10 / metabolism
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Chemokine CXCL9 / metabolism
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Dendritic Cells / physiology*
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Disease Models, Animal
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Humans
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Malaria, Cerebral / immunology*
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Malaria, Cerebral / parasitology
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Malaria, Cerebral / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Monocytes / cytology
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Plasmodium berghei / immunology
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Receptors, CCR5 / metabolism
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Spleen / cytology
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Spleen / physiology*
Substances
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Antigens, Protozoan
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CCR5 protein, mouse
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Chemokine CXCL10
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Chemokine CXCL9
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Cxcl10 protein, mouse
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Cxcl9 protein, mouse
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Receptors, CCR5