Toll‐Like Receptor 2–Deficient Mice Are Highly Susceptible to<i>Streptococcus pneumoniae</i>Meningitis because of Reduced Bacterial Clearing and Enhanced Inflammation

Echchannaoui, Hakim; Frei, Karl; Schnell, Christian; Leib, Stephen L.; Zimmerli, Werner; Landmann, Régine

doi:10.1086/342845

Cited by 273 publications

(226 citation statements)

References 42 publications

(40 reference statements)

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“…Two recent reports investigated the role of TLR2 in pneumococcal meningitis in vivo and demonstrated an aggravated course in mice lacking TLR2 using a clinical severity score (20,21). One study provided survival data showing a 100% fatality rate in both TLR2 Ϫ/Ϫ and wt mice (21).…”

Section: Discussionmentioning

confidence: 99%

“…One study provided survival data showing a 100% fatality rate in both TLR2 Ϫ/Ϫ and wt mice (21). In both investigations, in which S. pneumoniae was injected intracisternally, differences between TLR2 Ϫ/Ϫ and wt mice in bacterial clearance were modest at best.…”

Section: Discussionmentioning

confidence: 99%

“…In the study by Koedel et al (20), TLR2 Ϫ/Ϫ mice displayed more pneumococci in their cerebellum and blood, but not in their spleen. The recruitment of neutrophils to the CNS and blood cytokine concentrations were unaltered (20,21). In contrast to this CNS infection model, we tried to reproduce the natural route of pulmonary infection and infected mice i.n.…”

Section: Discussionmentioning

confidence: 99%

“…However, peritoneal macrophages harvested from mice lacking functional TLR2 and/or TLR4 responded normally to S. pneumoniae, suggesting that, for activation of these cells, neither TLR2 nor TLR4 is required (20). Two investigations examined the role of TLR2 in host defense against S. pneumoniae in vivo, both making use of a meningitis model in which pneumococci were injected directly into the CNS (20,21). Both studies reported an increased disease severity in TLR2-deficient (TLR2 Ϫ/Ϫ ) mice together with a moderately elevated bacterial outgrowth in the CNS when compared with normal wild-type (wt) mice.…”

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confidence: 99%

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Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense

Knapp¹,

Wieland²,

Veer

et al. 2004

The Journal of Immunology

243

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Toll-like receptors (TLR) are crucial pattern recognition receptors in innate immunity. The importance of TLR2 in host defense against Gram-positive bacteria has been suggested by the fact that this receptor recognizes major Gram-positive cell wall components, such as peptidoglycan and lipoteichoic acid. To determine the role of TLR2 in pulmonary Gram-positive infection, we first established that TLR2 is indispensable for alveolar macrophage responsiveness toward Streptococcus pneumoniae. Nonetheless, TLR2 gene-deficient mice intranasally inoculated with S. pneumoniae at doses varying from nonlethal (with complete clearance of the infection) to lethal displayed only a modestly reduced inflammatory response in their lungs and an unaltered antibacterial defense when compared with normal wild-type mice. These data suggest that TLR2 plays a limited role in the innate immune response to pneumococcal pneumonia, and that additional pattern recognition receptors likely are involved in host defense against this common respiratory pathogen.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense

Knapp¹,

Wieland²,

Veer

et al. 2004

The Journal of Immunology

243

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“…When compared with the WT mice the TLR2 knockout mice had greater bacterial loads in the brain, indicating that TLR2 conferred protective immunity against streptococcus pneumoniae infection in the CNS [103,104].…”

Section: Tlrs In Response To Bacterial Meningitismentioning

confidence: 95%

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

132

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A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses andare also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.

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Evaluation of Importance of Toll-like Receptor 4 in Acute Streptococcus pneumoniae Sinusitis in Mice

Luxameechanporn

Kirtsreesakul²,

Klemens³

et al. 2005

Arch Otolaryngol Head Neck Surg

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To investigate the effect of RC-527, a synthetic toll-like receptor 4 (TLR4) agonist, on stimulating the immune response before acute Streptococcus pneumoniae sinusitis in a mouse model, and to determine the importance of TLR4 in modulating the response to S pneumoniae. Toll-like receptor 4 agonists have been shown to induce protective innate immune responses when administered before some bacterial or viral challenges in mice. Design: We intranasally inoculated BALB/c, TLR4 complex-deficient C3H/HeJ, and wild-type C3H/HeOuJ mice with S pneumoniae 24 hours after treatment with 10 or 1 µg of RC-527 or vehicle. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were quantified at postinoculation days 2, 5, and 14. Main Outcome Measure: Immune response induced by RC-527. Results: Treatment with RC-527 induced an immune response through TLR4, as demonstrated by recruitment of phagocytes in uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. The immune response was also demonstrated by a significant increase of CD3 ϩ , CD4 ϩ , and CD8 ϩ T cells in infected and uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. However, the enhancement of the immune response induced by the TLR4 agonist showed a limited effect on bacterial clearance. Conclusions: Our studies in mice suggest that stimulation of TLR4 plays a minor role in the overall response to S pneumoniae infection of the upper airway, and stimulating this receptor before infection does not significantly enhance the immune response of immunocompetent mice to clear S pneumoniae infection.

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Toll‐Like Receptor 2–Deficient Mice Are Highly Susceptible toStreptococcus pneumoniaeMeningitis because of Reduced Bacterial Clearing and Enhanced Inflammation

Cited by 273 publications

References 42 publications

Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense

Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Evaluation of Importance of Toll-like Receptor 4 in Acute Streptococcus pneumoniae Sinusitis in Mice

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