The nucleotide-binding oligomerization domain-containing-2 ligand muramyl dipeptide enhances phagocytosis and intracellular killing of Escherichia coli K1 by Toll-like receptor agonists in microglial cells

Increasing the phagocytic activity of microglia could improve the resistance of immunocompromised patients to CNS infections. We studied the microglial responses upon stimulation with the Nod2 ligand muramyl dipeptide (MDP) alone or in combination with a TLR1/2, 3 or 4 agonist. MDP caused a mild release of NO, but induced neither a significant release of pro-inflammatory cytokines nor an expression of molecules associated with professional antigen presentation. Using the Escherichia coli K1 model, microglial pre-stimulation with MDP enhanced bacterial phagocytosis which was strengthened on TLR-pre-stimulated cells. Dual pre-stimulation of Nod2 and TLR1/2 or 4 caused maximal phagocytosis and intracellular killing.