Signalling of Toll-Like Receptors

Brikos, Constantinos; O’Neill, Luke A.J.

doi:10.1007/978-3-540-72167-3_2

Cited by 135 publications

(113 citation statements)

References 168 publications

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“…Several TLR genes were found to be 1.5-to 3-fold upregulated in this study; these included TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, TLR9, TLR10, out of which TLR7 was 3-fold upregulated. TLRs are generally grouped into two main groups based on the recognition of pathogen-associated molecular patterns (PAMPS) from invading agents: the first group comprises TLR1, TLR2, TLR4, and TLR6 and recognizes PAMPS from lipids; the second group consists of TLR3, TLR7, TLR8, and TLR9 that recognizes PAMPS from nucleic acids (Brikos and O'Neill 2008). TLR signaling leads to the activation of innate and adaptive immunity.…”

Section: Heat Stress Regulates Genes Involved In Immune Response and mentioning

confidence: 99%

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

Srikanth

Kwon

Lee

2017

Cell Stress and Chaperones

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This study aimed to investigate the genes and pathways that respond to heat stress in Holstein bull calves exposed to severe ranges of temperature and humidity. A total of ten animals from 4 to 6 months of age were subjected to heat stress at 37°C and 90 % humidity for 12 h. Skin and rectal temperatures were measured before and after heat stress; while no correlation was found between them before heat stress, a moderate correlation was detected after heat stress, confirming rectal temperature to be a better barometer for monitoring heat stress. RNAseq analysis identified 8567 genes to be differentially regulated, out of which 465 genes were significantly upregulated (≥2-fold, P < 0.05) and 49 genes were significantly downregulated (≤2-fold, P < 0.05) in response to heat stress. Significant terms and pathways enriched in response to heat stress included chaperones, cochaperones, cellular response to heat stress, phosphorylation, kinase activation, immune response, apoptosis, Toll-like receptor signaling pathway, Pi3K/AKT activation, protein processing in endoplasmic reticulum, interferon signaling, pathways in cancer, estrogen signaling pathway, and MAPK signaling pathway. The differentially expressed genes were validated by quantitative realtime PCR analysis, which confirmed the tendency of the expression. The genes and pathways identified in this analysis extend our understanding of transcriptional response to heat stress and their likely functioning in adapting the animal to hyperthermic stress. The identified genes could be used as candidate genes for association studies to select and breed animals with improved heat tolerance.

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Section: Heat Stress Regulates Genes Involved In Immune Response and mentioning

confidence: 99%

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

Srikanth

Kwon

Lee

2017

Cell Stress and Chaperones

View full text Add to dashboard Cite

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“…Simultaneously, the data reveal an increased expression of several interferoninducible genes, including guanylate binding protein 1 and 2, interferon alpha-inducible protein 6 and 27, ISG15 ubiquitin-like modifier and 2 0 ,5 0 -oligoadenylate synthetase 1 (see Table 3), which might illustrate the induction of interferon responses upon activation of pattern recognition receptors pathways. 20,21 Intriguingly, a distinct gene expression profile between TB and LTBI was observed when analysing expression of well-defined subsets of macrophage-and NK cell-associated genes. Macrophage-associated genes were upregulated in TB Host gene expression profiles in tuberculosis J Maertzdorf et al patients, whereas NK cell-associated genes were downregulated in TB patients as compared with LTBI patients (Table 3, list of cell-type-associated genes in part derived from Gaucher et al 22 ).…”

Section: Unique Expression Profiles In Tb Disease and Ltbimentioning

confidence: 99%

Human gene expression profiles of susceptibility and resistance in tuberculosis

et al. 2010

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Tuberculosis (TB) still poses a profound burden on global health, owing to significant morbidity and mortality worldwide. Although a fully functional immune system is essential for the control of Mycobacterium tuberculosis infection, the underlying mechanisms and reasons for failure in part of the infected population remain enigmatic. Here, whole-blood microarray gene expression analyses were performed in TB patients and in latently as well as uninfected healthy controls to define biomarkers predictive of susceptibility and resistance. Fc gamma receptor 1B (FCGRIB)was identified as the most differentially expressed gene, and, in combination with four other markers, produced a high degree of accuracy in discriminating TB patients and latently infected donors. We determined differentially expressed genes unique for active disease and identified profiles that correlated with susceptibility and resistance to TB. Elevated expression of innate immune-related genes in active TB and higher expression of particular gene clusters involved in apoptosis and natural killer cell activity in latently infected donors are likely to be the major distinctive factors determining failure or success in controlling M. tuberculosis infection. The gene expression profiles defined in this study provide valuable clues for better understanding of progression from latent infection to active disease and pave the way for defining predictive correlates of protection in TB.

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“…12 On activation, TLRs exert their inflammatory response through nuclear factor-B (NF-B) translocation to the nucleus. 13 Therefore, inhibition of TLRs may provide new therapeutic options after MI. This view is supported by recent observations in TLR-knockout mice.…”

Section: Clinical Perspective On P 90mentioning

confidence: 99%

Myocardial Ischemia/Reperfusion Injury Is Mediated by Leukocytic Toll-Like Receptor-2 and Reduced by Systemic Administration of a Novel Anti–Toll-Like Receptor-2 Antibody

et al. 2010

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Background-Reperfusion therapy for myocardial infarction is hampered by detrimental inflammatory responses partlyvia Toll-like receptor (TLR) activation. Targeting TLR signaling may optimize reperfusion therapy and enhance cell survival and heart function after myocardial infarction. Here, we evaluated the role of TLR2 as a therapeutic target using a novel monoclonal anti-TLR2 antibody. Method and Results-Mice underwent 30 minutes of ischemia followed by reperfusion. Compounds were administered 5 minutes before reperfusion. Cardiac function and dimensions were assessed at baseline and 28 days after infarction with 9.4-T mouse magnetic resonance imaging. Saline and IgG isotype treatment resulted in 34.5Ϯ3.3% and 31.4Ϯ2.7% infarction, respectively. Bone marrow transplantation experiments between wild-type and TLR2-null mice revealed that final infarct size is determined by circulating TLR2 expression. A single intravenous bolus injection of anti-TLR2 antibody reduced infarct size to 18.9Ϯ2.2% (Pϭ0.001). Compared with saline-treated mice, anti-TLR2-treated mice exhibited less expansive remodeling (end-diastolic volume 68.2Ϯ2.5 versus 76.8Ϯ3.5 L; Pϭ0.046) and preserved systolic performance (ejection fraction 51.0Ϯ2.1% versus 39.9Ϯ2.2%, Pϭ0.009; systolic wall thickening 3.3Ϯ6.0% versus 22.0Ϯ4.4%, Pϭ0.038). Anti-TLR2 treatment significantly reduced neutrophil, macrophage, and T-lymphocyte infiltration. Furthermore, tumor necrosis factor-␣, interleukin-1␣, granulocyte macrophage colony-stimulating factor, and interleukin-10 were significantly reduced, as were phosphorylated c-jun N-terminal kinase, phosphorylated p38 mitogen-activated protein kinase, and caspase 3/7 activity levels. Conclusions-Circulating TLR2 expression mediates myocardial ischemia/reperfusion injury. Antagonizing TLR2 just 5 minutes before reperfusion reduces infarct size and preserves cardiac function and geometry. Anti-TLR2 therapy exerts its action by reducing leukocyte influx, cytokine production, and proapoptotic signaling. Hence, monoclonal anti-TLR2 antibody is a potential candidate as an adjunctive for reperfusion therapy in patients with myocardial infarction. (Circulation. 2010;121:80-90.)Key Words: immune system Ⅲ inflammation Ⅲ myocardial infarction Ⅲ reperfusion Ⅲ Toll-like receptors E arly restoration of blood flow through the occluded coronary artery is currently the most effective therapy to limit infarct size and to preserve cardiac function and geometry after acute myocardial infarction (MI). 1 Nevertheless, reperfusion alone is insufficient to save endangered myocardium because complications resulting from loss of viable myocardium are still common after MI even after restoration of blood flow. Furthermore, studies have clearly demonstrated that reperfusion after ischemia causes additional cell death and increases infarct size (IS), called myocardial ischemia/reperfusion (I/R) injury. Many interventions aiming at reducing myocardial I/R injury have been proven to be successful in experimental studies but have failed in clinical se...

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Signalling of Toll-Like Receptors

Cited by 135 publications

References 168 publications

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

Human gene expression profiles of susceptibility and resistance in tuberculosis

Myocardial Ischemia/Reperfusion Injury Is Mediated by Leukocytic Toll-Like Receptor-2 and Reduced by Systemic Administration of a Novel Anti–Toll-Like Receptor-2 Antibody

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