Tumour necrosis factor alpha-induced neuronal loss is mediated by microglial phagocytosis

Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine, expressed in many brain pathologies and associated with neuronal loss. We show here that addition of TNF-alpha to neuronal-glial co-cultures increases microglial proliferation and phagocytosis, and results in neuronal loss that is prevented by eliminating microglia. Blocking microglial phagocytosis by inhibiting phagocytic vitronectin and P2Y(6) receptors, or genetically removing opsonin MFG-E8, prevented TNF-alpha induced loss of live neurons. Thus TNF-alpha appears to induce neuronal loss via microglial activation and phagocytosis of neurons, causing neuronal death by phagoptosis. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.