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.
Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany. sribes@med.uni-goettingen.de
Sandra
S
Ribes
Nina
N
Adam
Sandra
S
Schütze
Tommy
T
Regen
Sandra
S
Redlich
Hana
H
Janova
Angela
A
Borisch
Uwe-Karsten
UK
Hanisch
Roland
R
Nau
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
D000276:Adjuvants, Immunologic; D008024:Ligands; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D051193:Toll-Like Receptors; D000119:Acetylmuramyl-Alanyl-Isoglutamine