Toll-like receptor stimulation enhances phagocytosis and intracellular killing of nonencapsulated and encapsulated Streptococcus pneumoniae by murine microglia.
Toll-like receptors (TLRs) are crucial pattern recognition receptors in innate immunity that are expressed in microglia, the resident macrophages of the brain. TLR2, -4, and -9 are important in the responses against Streptococcus pneumoniae, the most common agent causing bacterial meningitis beyond the neonatal period. Murine microglial cultures were stimulated with agonists for TLR1/2 (Pam(3)CSK(4)), TLR4 (lipopolysaccharide), and TLR9 (CpG oligodeoxynucleotide) for 24 h and then exposed to either the encapsulated D39 (serotype 2) or the nonencapsulated R6 strain of S. pneumoniae. After stimulation, the levels of interleukin-6 and CCL5 (RANTES [regulated upon activation normal T-cell expressed and secreted]) were increased, confirming microglial activation. The TLR1/2, -4, and -9 agonist-stimulated microglia ingested significantly more bacteria than unstimulated cells (P < 0.05). The presence of cytochalasin D, an inhibitor of actin polymerizaton, blocked >90% of phagocytosis. Along with an increased phagocytic activity, the intracellular bacterial killing was also increased in TLR-stimulated cells compared to unstimulated cells. Together, our data suggest that microglial stimulation by these TLRs may increase the resistance of the brain against pneumococcal infections.
Ribes
Sandra
S
Department of Geriatrics, Evang. Krankenhaus Göttingen-Weende, An der Lutter 24, D-37075 Göttingen, Germany.
Ebert
Sandra
S
Regen
Tommy
T
Agarwal
Amit
A
Tauber
Simone C
SC
Czesnik
Dirk
D
Spreer
Annette
A
Bunkowski
Stephanie
S
Eiffert
Helmut
H
Hanisch
Uwe-Karsten
UK
Hammerschmidt
Sven
S
Nau
Roland
R
D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
D018925:Chemokines; D051193:Toll-Like Receptors