Abstract
The intracerebral formation of inflammatory infiltrates is a complex process, which may be regulated by chemokines. This study defines the kinetics and cellular sources of T cell- and macrophage-attracting chemokines in murine Toxoplasma encephalitis (TE) by ribonuclease protection assay, reverse transcription-PCR, in situ hybridization, and immunohistochemistry. Whereas astrocytes were the major source of interferon (IFN)-gamma-inducible protein-10 (CRG-2/IP-10) and monocyte chemoattractant protein (MCP)-1, microglia expressed RANTES, monokine induced by IFN-gamma (MuMIG) and occasionally CRG-2/IP-10 RNA. Despite being ubiquitously activated, only astrocytes and microglia confined to inflammatory infiltrates expressed chemokine genes. Intracerebral leukocytes transcribed RANTES, MuMIG, and occasionally CRG-2/IP-10 and MCP-1. IFN-gamma-deficient mice failed to produce CRG-2/IP-10, MuMIG, RANTES and expressed macrophage inflammatory protein (MIP-1)alpha, MIP-1 beta, and MCP-1 mRNA at reduced levels, functionally resulting in a strongly reduced recruitment of leukocytes across the blood-brain barrier and prevented their further invasion of the brain parenchyma. Since T cells are the single source of IFN-gamma in TE, these findings indicate that T cells pave the way of leukocytes to parenchymatous parasites via IFN-gamma.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Astrocytes / immunology
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Astrocytes / parasitology
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Astrocytes / pathology
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Brain / immunology*
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Brain / parasitology
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Brain / pathology
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Chemokine CCL2 / genetics
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Chemokine CCL2 / immunology
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Chemokine CCL4
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Chemokine CCL5 / genetics
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Chemokine CCL5 / immunology
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Chemokine CXCL10
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Chemokine CXCL9
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Chemokines / genetics
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Chemokines / immunology*
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Chemokines, CXC / genetics
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Chemokines, CXC / immunology
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Encephalitis / immunology*
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Encephalitis / parasitology
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Encephalitis / pathology
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Endothelium, Vascular / immunology
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / pathology
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Female
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Interferon-gamma / deficiency
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Interferon-gamma / genetics
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Interferon-gamma / immunology*
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Leukocytes / immunology*
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Leukocytes / parasitology
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Leukocytes / pathology
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Macrophage Inflammatory Proteins / genetics
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Macrophage Inflammatory Proteins / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Microglia / immunology
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Microglia / parasitology
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Monokines / genetics
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Monokines / immunology
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Neuroglia / immunology*
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Neuroglia / parasitology
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Neuroglia / pathology
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RNA, Messenger / immunology
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RNA, Messenger / metabolism
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Toxoplasmosis, Animal / immunology*
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Toxoplasmosis, Animal / pathology
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Toxoplasmosis, Animal / physiopathology
Substances
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Chemokine CCL2
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Chemokine CCL4
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Chemokine CCL5
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Chemokine CXCL10
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Chemokine CXCL9
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Chemokines
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Chemokines, CXC
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Cxcl10 protein, mouse
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Cxcl9 protein, mouse
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Macrophage Inflammatory Proteins
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Monokines
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RNA, Messenger
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Interferon-gamma