Treatment with Granulocyte-Macrophage Colony-Stimulating Factor Reduces Viral Titers in the Brains of West Nile Virus-Infected Mice and Improves Survival

Stonedahl, Sarah; Leser, J. Smith; Clarke, Penny; Potter, Huntington; Boyd, Timothy; Tyler, Kenneth L.

doi:10.1128/jvi.01805-22

Cited by 6 publications

(1 citation statement)

References 73 publications

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“…During encephalitis caused by West Nile virus (WNV), a re-emerging mosquito-borne neurotropic flavivirus, ablation of microglia via pharmacological inhibition of CSF1R also leads to loss of virologic control and increased mortality [12]. Indeed, subcutaneous administration of granulocyte-macrophage colony-stimulating factor, a ligand for CSF2R, significantly improves survival in mice peripherally infected with WNV (65% compared to 20% in vehicle-treated controls), with associated microglia activation and expression of C-C Motif chemokine ligand 2 and interleukin 6 (IL-6) [24 ▪▪ ], which have established roles in trafficking of leukocytes to sites of infection. Similarly, microglial depletion using CSF1R inhibition significantly increases mortality from Herpes Simplex Virus-1 (HSV1) encephalitis in mice [25].…”

Section: Microglia Functions In the Healthy Brainmentioning

confidence: 99%

Microglia at the scene of the crime: what their transcriptomics reveal about brain health

Arutyunov

Klein

2023

Current Opinion in Neurology

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Purpose of reviewMicroglia, which arise from primitive myeloid precursors that enter the central nervous system (CNS) during early development, are the first responders to any perturbance of homeostasis. Although their activation has become synonymous with neurologic disease, it remains unclear whether microglial responses are the cause of or response to neuropathology. Here, we review new insights in the roles of microglia during CNS health and disease, including preclinical studies that transcriptionally profile microglia to define their functional states.Recent findingsConverging evidence suggests that innate immune activation of microglia is associated with overlapping alterations in their gene expression profiles regardless of the trigger. Thus, recent studies examining neuroprotective microglial responses during infections and aging mirror those observed during chronic neurologic diseases, including neurodegeneration and stroke. Many of these insights derive from studies of microglial transcriptomes and function in preclinical models, some of which have been validated in human samples. During immune activation, microglia dismantle their homeostatic functions and transition into subsets capable of antigen presentation, phagocytosis of debris, and management of lipid homeostasis. These subsets can be identified during both normal and aberrant microglial responses, the latter of which may persist long-term. The loss of neuroprotective microglia, which maintain a variety of essential CNS functions, may therefore, in part, underlie the development of neurodegenerative diseases.SummaryMicroglia exhibit a high level of plasticity, transforming into numerous subsets as they respond to innate immune triggers. Chronic loss of microglial homeostatic functions may underlie the development of diseases with pathological forgetting.

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Section: Microglia Functions In the Healthy Brainmentioning

confidence: 99%