Toll-Like Receptor Stimulation Enhances Phagocytosis and Intracellular Killing of Nonencapsulated and Encapsulated Streptococcus pneumoniae by Murine Microglia

• Published in: Infection and Immunity Vol. 78; no. 2; pp. 865 - 871
• Main Authors: Ribes, Sandra, Ebert, Sandra, Regen, Tommy, Agarwal, Amit, Tauber, Simone C, Czesnik, Dirk, Spreer, Annette, Bunkowski, Stephanie, Eiffert, Helmut, Hanisch, Uwe-Karsten, Hammerschmidt, Sven, Nau, Roland
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.02.2010; American Society for Microbiology (ASM)
• Subjects: Animals; Bacteriology; Biological and medical sciences; Cells, Cultured; Chemokines - biosynthesis; Chemokines - immunology; Fundamental and applied biological sciences. Psychology; Host Response and Inflammation; Mice; Microbiology; Microglia - immunology; Microglia - metabolism; Microglia - microbiology; Microscopy, Confocal; Miscellaneous; Phagocytosis - immunology; Pneumococcal Infections - immunology; Pneumococcal Infections - metabolism; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism; Neuroglia; Rodentia; Toll like receptor; Immunity; Microglia; Streptococcus pneumoniae; Streptococcaceae; Vertebrata; Mammalia; Mouse; Bacteria; Micrococcales; Intracellular; Phagocytosis
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01110-09

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 (Pam₃CSK₄), 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.