M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

Background: microglia are the primary immune cells of the brain whose phenotype largely depends on their surrounding micro-environment. microglia respond to a multitude of soluble molecules produced by a variety of brain cells. macrophage colony-stimulating factor (m-csf) is a cytokine found in the brain whose receptor is expressed by microglia. previous studies suggest a critical role for m-csf in brain development and normal functioning as well as in several disease processes involving neuroinflammation.methods: using biopsy tissue from patients with intractable temporal epilepsy and autopsy tissue,we cultured primary adult human microglia to investigate their response to m-csf. mixed glial cultures were treated with 25 ng/ml m-csf for 96 hours. proliferation and phagocytosis assays,and high through-put immunocytochemistry,microscopy and image analysis were performed to investigate microglial phenotype and function.results: we found that the phenotype of primary adult human microglia was markedly changed following exposure to m-csf. a greater number of microglia were present in the m-csf- treated cultures as the percentage of proliferating (brdu and ki67-positive) microglia was greatly increased. a number of changes in protein expression occurred following m-csf treatment,including increased transcription factors pu.1 and c/ebpβ,increased dap12 adaptor protein,increased m-csf receptor (csf-1r) and igf-1 receptor,and reduced hla-dp,dq,dr antigen presentation protein. furthermore,a distinct morphological change was observed with elongation of microglial processes. these changes in phenotype were accompanied by a functional increase in phagocytosis of aβ1-42 peptide.conclusions: we show here that the cytokine m-csf dramatically influences the phenotype of adult human microglia. these results pave the way for future investigation of m-csf-related targets for human therapeutic benefit. © 2013 smith et al.; licensee biomed central ltd.