Tolerance induced by the TLR2 agonist bacterial lipoprotein (BLP) has been shown to attenuate the inflammatory response, and simultaneously to augment antimicrobial function, thereby conferring its protection against microbial sepsis.
Overall, our study provides a suggestion that TLRs 2, 3, 4 and 7 are highly expressed in the kidneys of septic mice and especially that these TLRs are sensitive and specific markers for sepsis.
However, the response to a TLR2 ligand is muted in cohoused mice, whereas the response to a TLR4 ligand is greatly amplified, suggesting a basis for the distinct response to Listeria monocytogenes and sepsis.
We also demonstrated blockade of intracellular signaling from TLR4 and TLR2 by thiol-modifying compounds which suggest a novel therapeutic intervention for sepsis, hyperoxia-induced cell injury and yeast infection.
Toll-like receptor 2 (TLR2) is currently investigated as a potential therapeutic target in diseases with underlying inflammation like sepsis and arthritis.
However, early-onset sepsis in term babies is caused by gram-positive species in more than 90% of cases, and neuro-inflammatory responses triggered through the gram-negative route (Toll-like receptor 4, TLR-4) are different from those induced through the gram-positive route via TLR-2.
In addition, subgroup analyses based on age group, ethnicity, sepsis type, and source of control also showed a significant effect of the TLR2Arg753Gln polymorphism on sepsis risk.
Polymorphisms of the toll-like receptor 2 and 4 genes are associated with faster progression and a more severe course of sepsis in critically ill patients.
The aim of this study was to investigate the associations between expression of TLR2, TLR4 and TLR9 and occurrence of sepsis in patients treated with intensive induction chemotherapy for AML.
This study suggests that endothelial TLR2 may be an important regulator of neutrophil trafficking to sites of infection in general, and that direct activation of lung endothelial TLR2 may contribute to acute lung injury during sepsis.
Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodulator secreted by the filarial nematode Acanthocheilonema viteae.
We investigated the supposed-2029C>T and 2258G>A TLR2 polymorphisms in 422 critically ill patients of European origin from southern Brazil (295 with sepsis and 127 without sepsis) and reviewed 33 studies on these polymorphisms, conducting a quality assessment with a score system.
To validate the concept of TLR4-targeted treatment strategies in gram-negative sepsis, we first showed that TLR4(-/-) and myeloid differentiation primary response gene 88 (MyD88)(-/-) mice were fully resistant to Escherichia coli-induced septic shock, whereas TLR2(-/-) and wild-type mice rapidly died of fulminant sepsis.
Previous study from our laboratory has demonstrated that in a setting of sepsis, toll-like receptor-4 (TLR4) signaling can induce TLR2 expression in endothelial cells (ECs), thereby increasing the cells' response to TLR2 ligands.
Single nucleotide polymorphisms (SNPs) Arg753Gln and Arg677Trp affect TLR2 responsiveness and may contribute to the course of sepsis, which is associated with substantial morbidity and mortality during intensive care treatment.
The TLR-2 genotypes (A/G) were considered a sepsis risk marker as compared with A/A (62.5% versus 37.5%, p < 0.03; relative risk = 2.5) in African American patients.
Single nucleotide polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of positive bacterial cultures and sepsis but not with altered prevalence of septic shock or decreased 28-day survival.