Online citations, reference lists, and bibliographies.
← Back to Search

Toll-Like Receptor Stimulation Enhances Phagocytosis And Intracellular Killing Of Nonencapsulated And Encapsulated Streptococcus Pneumoniae By Murine Microglia

S. Ribes, S. Ebert, T. Regen, A. Agarwal, S. Tauber, D. Czesnik, A. Spreer, S. Bunkowski, H. Eiffert, U. Hanisch, S. Hammerschmidt, R. Nau
Published 2009 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
ABSTRACT 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.
This paper references
Toll-Like Receptor 2 Deficiency Delays Pneumococcal Phagocytosis and Impairs Oxidative Killing by Granulocytes
M. Letiembre (2005)
Central nervous system infection in the immunocompromised host, p. 163–214
A. R. Tunkel (2002)
Clinical Approach to Infection in the Compromised Host
R. Rubin (1994)
Toll‐like receptor 9 acts at an early stage in host defence against pneumococcal infection
B. Albiger (2007)
Innate immunity: the missing link in neuroprotection and neurodegeneration?
M. Nguyen (2002)
Meningeal and Perivascular Macrophages of the Central Nervous System Play a Protective Role During Bacterial Meningitis
M. M. Polfliet (2001)
Microglia: a sensor for pathological events in the CNS
G. Kreutzberg (1996)
Microglia in Infectious Diseases of the Central Nervous System
Monica M. Mariani (2009)
Toll-like Receptors in Defense and Damage of the Central Nervous System
R. Aravalli (2007)
pMV 158 GFP , a derivative of pMV 158 that carries the gene encoding the green fluorescent protein
F. Kirchhoff (2005)
Acute bacterial meningitis in adults. A review of 493 episodes.
M. Durand (1993)
Construction of the mobilizable plasmid pMV158GFP, a derivative of pMV158 that carries the gene encoding the green fluorescent protein.
C. Nieto (2003)
Topical resiquimod 0.01% gel decreases herpes simplex virus type 2 genital shedding: a randomized, controlled trial.
K. Mark (2007)
Toll-like receptors in brain abscess.
N. Esen (2009)
Toll-Like Receptor Prestimulation Increases Phagocytosis of Escherichia coli DH5α and Escherichia coli K1 Strains by Murine Microglial Cells
S. Ribes (2008)
MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses
S. Garg (2009)
Microglia as a source and target of cytokines
U. Hanisch (2002)
Central nervous system infections in cancer patients.
A. Pruitt (2004)
MyD88-dependent immune response contributes to hearing loss in experimental pneumococcal meningitis.
M. Klein (2007)
Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases.
S. Kastenbauer (2003)
Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo
Axel Nimmerjahn (2005)
Minimal penetration of lipopolysaccharide across the murine blood–brain barrier
W. Banks (2010)
Bacterial and fungal meningitis in patients with cancer
J. Safdieh (2008)
Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation.
H. Echchannaoui (2002)
Macrophage and microglial responses to cytokines in vitro: Phagocytic activity, proteolytic enzyme release, and free radical production
M. Smith (1998)
Toll-like receptors.
H. S. Warren (2005)
Pneumococcal Virulence Gene Expression and Host Cytokine Profiles during Pathogenesis of Invasive Disease
L. K. Mahdi (2007)
Differential production of and migratory response to beta chemokines by human microglia and astrocytes.
P. Peterson (1997)
Effect of thalidomide on chemokine production by human microglia.
J. Lokensgard (2000)
MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS.
U. Koedel (2004)
Toll-like receptors as potential therapeutic targets for multiple diseases
C. Zuany-Amorim (2002)
Innate immunity and the pneumococcus.
G. Paterson (2006)
Mechanism of action of imiquimod 5% cream in the treatment of anogenital warts.
Tyring (1998)
The pharmacology of endosomal TLR agonists in viral disease.
D. R. Averett (2007)
Effects of Systemic Immunogenic Insults and Circulating Proinflammatory Cytokines on the Transcription of the Inhibitory Factor κBα Within Specific Cellular Populations of the Rat Brain
N. Laflamme (1999)
Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination
S. Ebert (2005)
CD14 deficiency leads to increased MIP‐2 production, CXCR2 expression, neutrophil transmigration, and early death in pneumococcal infection
H. Echchannaoui (2005)
The Apoptotic Response to Pneumolysin Is Toll-Like Receptor 4 Dependent and Protects against Pneumococcal Disease
A. Srivastava (2005)
A Mechanism for Neurodegeneration Induced by Group B Streptococci through Activation of the TLR2/MyD88 Pathway in Microglia1
S. Lehnardt (2006)
Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series
M. Weisfelt (2006)
TLR9 agonists as adjuvants for prophylactic and therapeutic vaccines.
C. Daubenberger (2007)
Neuronal injury mediated via stimulation of microglial toll‐like receptor‐9 (TLR9)
A. Iliev (2004)
Myeloid differentiation factor 88‐dependent signalling controls bacterial growth during colonization and systemic pneumococcal disease in mice
B. Albiger (2005)
Central nervous system infections in the compromised host: a diagnostic approach.
B. Cunha (2001)
Activated microglia mediate neuronal cell injury via a nitric oxide mechanism.
C. Chao (1992)
Central Nervous System Infection in the Immunocompromised Host
A. Tunkel (1994)
Neuropsychological sequelae of bacterial and viral meningitis.
H. Schmidt (2006)
Thrombospondin‐1 promotes cellular adherence of Gram‐positive pathogens via recognition of peptidoglycan
C. Rennemeier (2007)

This paper is referenced by
Microglial diversity by responses and responders
Ulla Gertig (2014)
Strategies to increase the activity of microglia as efficient protectors of the brain against infections
R. Nau (2014)
Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 by macrophages and increases the resistance of mice against infections
Sandra Redlich (2014)
Infektionen und Nervensystem in der Geriatrie
Marija Djukic (2019)
Microglia: Brain cells on the move
S. Smolders (2019)
Microglia development and function.
Debasis Nayak (2014)
The Polysaccharide Capsule of Streptococcus pneumonia Partially Impedes MyD88-Mediated Immunity during Pneumonia in Mice
A. D. de Vos (2015)
Interferon-γ-Induced Nitric Oxide Synthase-2 Contributes to Blood/Brain Barrier Dysfunction and Acute Mortality in Experimental Streptococcus pneumoniae Meningitis.
B. Yau (2016)
Influences of Nanoparticles Characteristics on the Cellular Responses: The Example of Iron Oxide and Macrophages
Bastien Dalzon (2020)
This information is current as Phagocytosis after Bacterial Infection miR-15 a / 16 Regulates Macrophage
Hyung-geun Moon (2014)
Higher mortality and impaired elimination of bacteria in aged mice after intracerebral infection with E. coli are associated with an age-related decline of microglia and macrophage functions
Sandra Schütze (2014)
The Role of Microglia in Bacterial Meningitis: Inflammatory Response, Experimental Models and New Neuroprotective Therapeutic Strategies
Sigrun Thorsdottir (2019)
Alternatively Spliced Forms of Tollip Regulate Inflammatory Signalling in Macrophages
Yu-Lan Lo (2012)
Toll‐like receptor 4 deficiency impairs microglial phagocytosis of degenerating axons
Labchan Rajbhandari (2014)
Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases
A. Savva (2013)
Bright fluorescent Streptococcus pneumoniae for live-cell imaging of host-pathogen interactions.
M. Kjos (2015)
Vitamin D Deficiency Reduces the Immune Response, Phagocytosis Rate, and Intracellular Killing Rate of Microglial Cells
M. Djukic (2014)
Characterization of a pneumococcal meningitis mouse model
B. Mook-Kanamori (2012)
Current knowledge and future directions of TLR and NOD signaling in sepsis
N. Foley (2015)
Toll-Like Receptor 2 and Lipoprotein-Like Lipoproteins Enhance Staphylococcus aureus Invasion in Epithelial Cells
M. Nguyen (2018)
Single nucleotide polymorphisms in TLR9 are highly associated with susceptibility to bacterial meningitis in children.
M. Sanders (2011)
Construction of a plasmid vector based on the pMV158 replicon for cloning and inducible gene expression in Streptococcus pneumoniae.
J. A. Ruiz-Masó (2012)
Microglial clearance function: dependence on phenotypes
Ana Filipa Martins Oliveira (2011)
Stability of Alkyl Chain-Mediated Lipid Anchoring in Liposomal Membranes.
Lukas Gleue (2020)
miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection
Hyung-geun Moon (2014)
Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes
Chanyoung Song (2017)
Specific features of human monocytes activation by monophosphoryl lipid A
Ryme Chentouh (2018)
αEnv-decorated phosphatidylserine liposomes trigger phagocytosis of HIV-virus-like particles in macrophages.
Andrea Gramatica (2014)
Neuroinflammation in Ischaemic Stroke: Utilizing the Biphasic Niche of Neuroprotection and Neurotoxicity for Clinic
Mohammed A. Alam (2016)
Toll-Like Receptor 2–Mediated Autophagy Promotes Microglial Cell Death by Modulating the Microglial M1/M2 Phenotype
Kun Ma (2019)
Pneumococcal pep27 mutant immunization stimulates cytokine secretion and confers long-term immunity with a wide range of protection, including against non-typeable strains.
Gyu-Lee Kim (2016)
Pathophysiology of pneumococcal meningitis
M. Geldhoff (2016)
See more
Semantic Scholar Logo Some data provided by SemanticScholar