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

Department of Geriatrics, Evang. Krankenhaus Göttingen-Weende, An der Lutter 24, D-37075 Göttingen, Germany.
Infection and immunity (Impact Factor: 3.73). 11/2009; 78(2):865-71. DOI: 10.1128/IAI.01110-09
Source: PubMed


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.

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    • "Pneumococcal cell wall components, peptidoglycan and lipoteichoic acid, trigger the release of potent proinflammatory mediators by microglia (Hanisch and others 2001; Kochan and others 2012). In addition, microglia are of specific interest in PM due to their phagocytic properties: alongside surface TLR2 and TLR4 signaling, microglial phagocytosis of live pneumococci (Ribes and others 2010) also elicits proinflammatory responses, likely through TLR9 (Albiger and others 2007). The proinflammatory cytokine interferon-gamma (IFNg) is well studied in inflammation models (Schroder and others 2004; Schoenborn and Wilson 2007) and its signaling mechanisms have been reviewed by Schroder and others (2004). "

    Journal of Interferon & Cytokine Research 09/2015; DOI:10.1089/jir.2015.0078 · 2.00 Impact Factor
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    • "Since bacterial DNA, unlike eukaryotic DNA contains a high rate of unmethylated cytosine-guanine (CpG) motifs [29], recent attention has focused on this epitope, which is a ligand of Toll-like receptor (TLR)-9. Stimulation of microglial cells with CpG oligonucleotides increased phagocytosis of E. coli, Streptococcus pneumoniae and Cryptococcus neoformans and intracellular killing of these pathogens by microglial cells [30-32]. In various animal models, CpG ODN pre-treatment conferred protection against a variety of bloodstream and other extracerebral bacterial infections [33-35]. "
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    • "These agents also increased intracellular bacterial killing. The presence of a bacterial capsule as one important virulence factor decreased the rate of phagocytosis of E. coli and S. pneumoniae by one order of magnitude compared to unencapsulated strains (Ribes et al., 2009, 2010a,b, 2012). Agonists of the innate immune system also enhanced the phagocytosis of Cryptococcus neoformans (Redlich et al., 2013). "
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    Frontiers in Cellular Neuroscience 05/2014; 8:138. DOI:10.3389/fncel.2014.00138 · 4.29 Impact Factor
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