Fibronectin stimulates Escherichia coli phagocytosis by microglial cells.
Microglia express Toll-like receptors (TLRs) that recognize invading pathogens as well as endogenous proteins such as fibronectin under nonphysiological conditions. Here, we demonstrated that fibronectin stimulates murine microglia in culture in a dose-dependent manner: microglial cells secreted proinflammatory cytokines and chemokines and increased phagocytosis of Escherichia coli DH5alpha and E. coli K1 strains. Low levels of fibronectin exerted a synergistic effect on the release of proinflammatory compounds by microglia co-stimulated with agonists for TLR1/2 (Pam(3)CSK(4)) or TLR9 (CpG DNA), but not in combination with the TLR4 agonist lipopolysaccharide (LPS). Phagocytosis of bacterial strains was moderately enhanced when microglia was co-stimulated with high concentrations of fibronectin and one pathogen-derived TLR agonist. In conclusion, fibronectin increased proinflammatory and phagocytotic functions in microglia and partially synergized with microbial TLR agonists.
Ribes
Sandra
S
Department of Neurology, University of Göttingen, Robert-Koch-Strasse 40, Göttingen, Germany. sribes@med.uni-goettingen.de
Ebert
Sandra
S
Regen
Tommy
T
Czesnik
Dirk
D
Scheffel
Jörg
J
Zeug
Andre
A
Bunkowski
Stephanie
S
Eiffert
Helmut
H
Hanisch
Uwe-Karsten
UK
Hammerschmidt
Sven
S
Nau
Roland
R
D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D005911:Gliosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D051194:Toll-Like Receptor 1 / Q000819:agonists / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D005353:Fibronectins; D051194:Toll-Like Receptor 1; D051217:Toll-Like Receptor 9