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- W4313359909 abstract "Abstract In the brain, microglia are the resident immune cells. Despite their location in the brain parenchyma and expression of machinery capable of responding to pathogens, little is known about the role microglia play during infection. Toxoplasma gondii is an intracellular, protozoan parasite that establishes a chronic infection in the brain. T cell-derived IFN-g is central to control parasite replication and prevent host mortality by activating anti-parasitic mechanisms. In addition, during brain infection monocyte-derived macrophages (MDMs) enter the brain. Deciphering the contribution of these two cell populations during T. gondii infection has been confounded by their phenotypic and morphologic similarity. However, these cells likely contribute differently to parasite control. Using a reporter mouse to label microglia we have found that MDMs are the primary producers of nitric oxide, a key anti-parasitic molecule. Therefore, to explore the role of microglia and MDMs in the control of T. gondii in vivo we are taking advantage of constitutive or inducible cre recombinase activity driven from the CX3CR1 promoter which allow both microglia and MDMs or solely microglia, respectively, to be targeted genetically. By removing the gene STAT1 from these cells we have rendered them unable to upregulate key IFN-g induced genes necessary for controlling T. gondii. Mice in which MDMs and microglia are unresponsive to IFN-g are unable to control parasite replication and succumb to infection by 19dpi. Conversely, mice in which only microglia are deficient in IFN-g signaling do not succumb to infection and resemble infected control mice. These results suggest that microglia are not a key cell type responsible for controlling T. gondii in the CNS." @default.
- W4313359909 created "2023-01-06" @default.
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- W4313359909 date "2017-05-01" @default.
- W4313359909 modified "2023-10-14" @default.
- W4313359909 title "The role of microglia and monocyte-derived macrophages in <i>Toxoplasma gondii</i> infection of the brain" @default.
- W4313359909 doi "https://doi.org/10.4049/jimmunol.198.supp.68.16" @default.
- W4313359909 hasPublicationYear "2017" @default.
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