Bacterial meningitis still retains high rates of morbidity and mortality, and survivors often sustain debilitating neurological sequelae due to neuronal cell-death resulting from the infection. The pathophysiology of gram-positive bacterial meningitis can be simulated in vitro by application of the major cell-wall component lipoteichoic acid (LTA) – mimicking bacterial autolysis that occurs in vivo. This has been shown to result in loss of up to 50 % of cerebellar granule neurons in mixed neuronal-glial cultures. This effect presumably involved the phagocytosis of dying cells – a conclusion supported by the facts that dying cells were virtually absent in mixed cultures treated with LTA, and that cell-loss was not observed in pure neuronal cultures (lacking both microglia and astrocytes).¹ To test the contribution of phagocytosis to neuronal loss, cytochalasin D, a compound that inhibits phagocytosis by blocking F-actin polymerization, was added here concomitantly with LTA. Cytochalasin D fully prevented neuronal loss for up to 7 days after LTA-treatment. Also, analysis of the phagocytic capacity of pure microglial cultures revealed that LTA-stimulation resulted in enhanced phagocytosis of polystyrene microspheres. This effect could be partially inhibited by cytochalasin D, confirming both a stimulation of phagocytic activity as a response to LTA-treatment as well as the inhibitory action of cytochalasin D on this process. However, cytochalasin D also prevented microglial proliferation, which occurs in response to LTA. To exclude that the neuroprotective action of cytochalasin D was due to a side-effect, an alternative method to prove the importance of phagocytosis was used. First, microglia were selectively eliminated from mixed cultures by application of the lysosomotropic reagent, L-leucine-methyl-ester (LME) – a procedure that leaves the astrocyte population unaffected. This alone was sufficient to fully abolish neuronal loss in response to LTA. Alternatively, reconstitution of the culture system by addition of microglia to LME-treated cultures fully restored the original effect. However, when microglia were co-cultured in transwell-inserts, they were unable to induce neuronal death. Notably, microglial proliferation was observed in transwell-inserts – indicating that inflammatory microglial activation was still induced. Our results show that LTA enhances the phagocytic capacity of microglia and that the loss of cerebellar granule neurons in response to LTA is fully dependent on the presence of microglia. More specifically, under these conditions neuronal death is not induced by soluble mediators (such as e.g. the pro-inflammatory cytokine TNF-α) but by a contact-dependent neuronal-microglial interaction.