Impaired inflammatory responses to multiple Toll-like receptor ligands in alveolar macrophages of streptozotocin-induced diabetic mice

Objective  

To investigate the effect of hyperglycemic state on the activation of alveolar macrophages (AMs) mediated via Toll-like receptors (TLRs) typically associated with bacterial infection.     

Regulation of Toll-like receptor 1 and -2 in neonatal mice brains after hypoxia-ischemia

Background  

Hypoxic-ischemic (HI) brain injury remains a major problem in newborns, resulting in increased risk of neurological disorders. Neonatal HI triggers a broad inflammatory reaction in the brain, including activation of the innate immune system. Toll-like receptors (TLRs), which are key components of the innate immune system, are believed to play a role in adult cerebral ischemic injury. The expression of TLRs in the neonatal brain and their regulation after HI is unknown.     

TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate

Objective  

Neutrophil infiltration is a key regulator in the pathophysiology of acute pancreatitis (AP), although the impact of Toll-like receptors (TLRs) in AP remains elusive. The aim of this study was to define the role of TLR2 and TLR4 in leukocyte recruitment and tissue damage in severe AP.     

Increased Levels of the High Mobility Group Box 1 Protein Sustain the Inflammatory Bone Marrow Microenvironment in Patients with Chronic Idiopathic Neutropenia via Activation of Toll-Like Receptor 4

Purpose  

Chronic idiopathic neutropenia (CIN) is a granulocytic disorder characterized by increased apoptosis of the bone marrow (BM) granulocytic progenitor cells and an inflammatory BM microenvironment. The aim of this study was to investigate the possible involvement of Toll-like receptors (TLRs) in the production of pro-inflammatory mediators in CIN BM.     

Toll-like receptor 9 polymorphisms influence mother-to-child transmission of human immunodeficiency virus type 1

Background  

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and play a crucial role in the host's innate immune response. Genetic variations in TLR genes may influence host-viral interactions and might impact upon the risk of mother-to-child transmission (MTCT) of Human Immunodeficiency Virus type 1 (HIV-1). The aim of this study was to investigate the influence of genetic variants of TLR 9 gene on MTCT.     

Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy

Background  

The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.     

Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury

Background  

Toll like receptors (TLRs) signaling pathways, including the adaptor protein Mal encoded by the TIRAP gene, play a central role in the development of acute lung injury (ALI). Recently, the TIRAP variants have been described association with susceptibility to inflammatory diseases. The aim of this study was to investigate whether genetic variants in TIRAP are associated with the development of ALI.     

Genomic profile of Toll-like receptor pathways in traumatically brain-injured mice: effect of exogenous progesterone

Background  

Traumatic brain injury (TBI) causes acute inflammatory responses that result in an enduring cascade of secondary neuronal loss and behavioral impairments. It has been reported that progesterone (PROG) can inhibit the increase of some inflammatory cytokines and inflammation-related factors induced by TBI. Toll-like receptors (TLRs) play a critical role in the induction and regulation of immune/inflammatory responses. Therefore, in the present study, we examined the genomic profiles of TLR-mediated pathways in traumatically injured brain and PROG's effects on these genes.     

Evaluation of the toll-like receptor 6 Ser249Pro polymorphism in patients with asthma,atopic dermatitis and chronic obstructive pulmonary disease

Background  

For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis'). Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases. We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD).     

Toll-like receptor 4 can recognize SapC-DOPS to stimulate macrophages to express several cytokines

Objective and design  

SapC-DOPS is a newly combined compound consisting of saposin C and dioleoylphosphatidylserine (DOPS). Our recent study showed that SapC-DOPS exhibits anti-tumor activity. However, SapC-DOPS has recognition elements of Toll-like receptor (TLR) 2 and TLR4;therefore, we want to know whether SapC-DOPS can induce abnormal immunoreaction via identification TLRs.     

15-Deoxy-Δ<Superscript>12,14</Superscript>-Prostaglandin J<Subscript>2</Subscript> and Curcumin Modulate the Expression of Toll-like Receptors 4 and 9 in Autoimmune T Lymphocyte

Introduction

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model for multiple sclerosis (MS). We have shown earlier that 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) and curcumin ameliorate EAE by modulating inflammatory signaling pathways in T lymphocytes. Toll-like receptors (TLRs), expressed primarily in innate immune cells, play critical roles in the pathogenesis of EAE. T lymphocytes also express TLRs and function as costimulatory receptors to upregulate proliferation and cytokine production in response to specific agonists.

Discussion

In this study, we show that naïve CD4⁺ and CD8⁺ T cells express detectable levels of TLR4 and TLR9 and that increase after the induction of EAE in SJL/J and C57BL/6 mice by immunization with PLPp139–151 and MOGp35–55 antigen, respectively. It is interesting to note that in vivo treatment with 15d-PGJ2 or curcumin results in a significant decrease in TLR4 and TLR9 expression in CD4⁺ and CD8⁺ T cells in association with the amelioration of EAE.

Conclusion

Although the exact mechanisms are not known, the modulation of TLR expression in T lymphocytes by 15d-PGJ₂ and curcumin suggests new therapeutic targets in the treatment of T cell-mediated autoimmune diseases.

     

Decreased expression of toll like receptor signaling molecules in chronic HBV infected patients

Introduction

Toll like receptors (TLRs) and their signaling molecules play important roles in microbe recognition and induction of immune responses, including production of inflammatory cytokines, against viral infections. Therefore, the aim of this study was to examine expression levels of TLR signaling molecules (IRAK1, IRAK4, TRAF3, and IRF7) and the pro-inflammatory cytokines, IL-12 and IL-6 in chronic HBV infected (CHB) patients.

Design

This study was performed on 60 CHB patients and 60 healthy controls and the expression of IRAK1, IRAK4, TRAF3, and IRF7 and their downstream inflammatory cytokines (IL-12 and IL-6) were evaluated by Real-Time PCR and ELISA techniques.

Results

The results demonstrated that expression of IRAK4, TRAF3, and IRF7 were significantly decreased in PBMCs of CHB patients in comparison to healthy controls. Serum levels of IL-12 were significantly increased, while, IL-6 were not differ between patients and controls.

Conclusions

Based on the results presented here it seems that CHB patients do not express appropriate levels of the genes in the TLRs pathway which may lead to impaired immune responses against HBV infection which is seen in the patients.     

Scavenger receptors and β-glucan receptors participate in the recognition of yeasts by murine macrophages

Objectives  

Numerous receptors have been implicated in recognition of pathogenic fungi by macrophages, including the β-glucan receptor dectin-1. The role of scavenger receptors (SRs) in anti-fungal immunity is not well characterized.     

Innate Immune Detection of Bacterial Virulence Factors Via the NLRC4 Inflammasome

Introduction  

Cytokine production by innate immune cells is initiated by signaling downstream of pattern recognition receptors, including Toll-like receptors.     

Peripheral muscarinic receptors mediate the anti-inflammatory effects of auricular acupuncture

Background  

The cholinergic and opioid systems play important roles in modulating inflammation. This study tests whether auricular acupuncture (AA) produces anti-inflammatory effects via opioid and peripheral cholinergic receptors in a rat model.     

Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis

Objective and design

Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues.

Materials and methods

Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10⁶ cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR.

Results

We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group.

Conclusions

In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.