Chemokines are differentially expressed by astrocytes, microglia and inflammatory leukocytes in Toxoplasma encephalitis and critically regulated by interferon-gamma.
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.
Strack
Andreas
A
Abteilung für Neuropathologie, Universität zu Köln, Joseph-Stelzmann-Str. 9, 50931 Köln, Germany.
Asensio
Valérie C
VC
Campbell
Iain L
IL
Schlüter
Dirk
D
Deckert
Martina
M
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D001921:Brain / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000235:genetics / Q000276:immunology*; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000469:parasitology; D015846:Monokines / Q000235:genetics / Q000276:immunology; D009457:Neuroglia / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D007371:Interferon-gamma