scholarly journals Peptidoglycan of Staphylococcus aureus Upregulates Monocyte Expression of CD14, Toll-Like Receptor 2 (TLR2), and TLR4 in Human Blood: Possible Implications for Priming of Lipopolysaccharide Signaling

2005 ◽  
Vol 73 (11) ◽  
pp. 7613-7619 ◽  
Author(s):  
J. S. Hadley ◽  
J. E. Wang ◽  
S. J. Foster ◽  
C. Thiemermann ◽  
C. J. Hinds
Keyword(s):  
Human Blood ◽  
Priming Effect ◽  
Ex Vivo ◽  
Experimental Period ◽  
Cytokine Release ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Twofold Increase ◽  
Toll Like Receptor 2

ABSTRACT Previous studies have indicated that peptidoglycan (PepG) from gram-positive bacteria can exert a priming effect on the innate immune response to lipopolysaccharide (LPS) from gram-negative bacteria. Here, we hypothesized that this priming effect may be preceded by enhanced expression of monocyte CD14, Toll-like receptor 2 (TLR2), and TLR4. In an ex vivo whole human blood model, we observed a substantial synergy between LPS and PepG in the release of tumor necrosis factor alpha and interleukin-1β (IL-1β) over the 24-h experimental period, whereas the effect on IL-8 and IL-10 release was more time dependent. The priming effect of PepG on cytokine release was preceded by a rapid upregulation of CD14, TLR2, and TLR4 expression on monocytes: at 3 hours there was a twofold increase in CD14 expression (P < 0.03), a fivefold increase in TLR2 expression (P < 0.03), and a twofold increase in TLR4 expression (P < 0.03). CD14 and TLR2 remained upregulated throughout the experimental period following exposure to PepG (P < 0.05). Only a transient upregulation of these monocyte receptors was observed following treatment with LPS or LPS plus PepG. In conclusion, the synergistic effect of LPS and PepG on cytokine release is preceded by a reciprocal upregulation of TLR2 and TLR4 by both bacterial cell wall components.

scholarly journals Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

2011 ◽  
Vol 13 (1) ◽  
Author(s):  
Sinéad Nic An Ultaigh ◽  
Tajvur P Saber ◽  
Jennifer McCormick ◽  
Mary Connolly ◽  
Jerome Dellacasagrande ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ex Vivo ◽  
Cytokine Release ◽  
Toll Like Receptor ◽  
Explant Cultures ◽  
Toll Like Receptor 2

scholarly journals Decreased Toll-like Receptor (TLR) 2 and 4 Expression in Spermatozoa in Couples with Unexplained Recurrent Spontaneous Abortion (URSA)

2020 ◽  
Author(s):  
Nasrin Sereshki ◽  
Alireza Andalib ◽  
Ataollah Ghahiri ◽  
Ferdos Mehrabian ◽  
Roya Sherkat ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Toll Like Receptor 2 ◽  
And Control ◽  
Reproductive Processes

Studies have shown that toll-like receptors (TLRs) play some important roles in reproductive processes such as ovulation, spermatogenesis, sperm capacitation, fertilization, and pregnancy to the best of our knowledge, no study has evaluated the expression and role of these molecules and their impairment in spermatozoa; accompanied by pregnancy complications such as recurrent spontaneous abortion (RSA). Therefore, this study investigates the alteration of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) expression in spermatozoa in men whose spouse have unexplained RSA. Fifteen fertile couples and fifteen couples with unexplained recurrent spontaneous abortion (URSA) were included in this study. The level of TLR2 and TLR4 expression in untreated and lipopolysaccharide (LPS) or PAM3CYS in treated spermatozoa were examined by flow cytometry. The results showed reduced expression of TLR4 in untreated spermatozoa and decreased LPS or PAM3CYS levels in treated spermatozoa in the URSA group compared to the control group. No significant differences were found in TLR2 expression of untreated spermatozoa in RSA and control groups. After the treatment of spermatozoa with LPS, the TLR2 expression was decreased in both groups. After the treatment of spermatozoa with PAM3CYS, the level of TLR2 expression was significantly increased in the URSA group; while no significant differences were shown in the control group in comparison to untreated spermatozoa. We have concluded that decreased TLR4 expression and a differently increased TLR2 expression in response to ligand treatment in spermatozoa is associated with URSA.

scholarly journals Intrarenal Toll-like receptor 4 and Toll-like receptor 2 expression correlates with injury in antineutrophil cytoplasmic antibody-associated vasculitis

2018 ◽  
Vol 315 (5) ◽  
pp. F1283-F1294 ◽  
Author(s):  
Kim M. O’Sullivan ◽  
Sharon L. Ford ◽  
Anthony Longano ◽  
A. Richard Kitching ◽  
Stephen R. Holdsworth
Keyword(s):  
Renal Injury ◽  
Estimated Glomerular Filtration Rate ◽  
High Mobility ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Toll Like Receptor 4 ◽  
Toll Like Receptor 2 ◽  
Functional Relevance

In antineutrophil cytoplasmic antibody-associated vasculitis (AAV), Toll-like receptors (TLRs) may be engaged by infection-associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4, and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4, and TLR9, with TLR4 being the most prominent in both compartments. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression and the intensity of glomerular TLR2 expression inversely correlated with the presenting estimated glomerular filtration rate. Although myeloid cells within the kidney expressed TLR2, TLR4, and TLR9, TLR2 and TLR4 colocalized with endothelial cells and podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional relevance of intrarenal TLR expression was further supported by the colocalization of TLRs with their endogenous ligands high-mobility group box 1 and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 expression and their correlation with renal injury indicates that TLR4, and to a lesser degree TLR2, may be potential therapeutic targets in this disease.

scholarly journals Toll-Like Receptor 2 Expression as a New Hallmark of Advanced Endometriosis

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1813 ◽  
Author(s):  
Małgorzata Sobstyl ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Ewelina Grywalska ◽  
Izabela Korona-Głowniak ◽  
Anna Sobstyl ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Lymphocytes ◽  
Characteristic Curve ◽  
Cost Effective ◽  
Peripheral Blood Lymphocytes ◽  
Toll Like Receptor ◽  
Myeloid Dendritic Cells ◽  
Tlr2 Expression ◽  
Toll Like Receptor 2 ◽  
Effective Diagnosis

Recent evidence suggests that immunological aspects play a pivotal role in this disorder. Toll-like receptor 2 (TLR2) is crucial in recognizing microbial infections and mediating innate immune response. The objective of our study was to rate with flow cytometry the levels of several subsets of dendritic cells, monocytes, and basic peripheral blood lymphocytes expressing TLR2, aiming at the determination of a possible correlation between the expression of TLR2 and the clinical outcomes of endometriosis in 40 patients and 40 age-matched healthy women. Our study showed the importance of TLR2 expression, mainly on myeloid dendritic cells (mDCs) and B cells in patients with endometriosis. Both mDCs BDCA1+CD19-TLR2+ and B lymphocytes CD19+TLR-2+ proved useful in the differentiation of affected individuals with stages 3–4 of the disease (area under the receiver operating characteristic curve /AUC/ = 0.96, p < 0.0001 for mDCs; AUC = 0.78, p = 0.0001 for B lymphocytes), and those presenting adhesion (AUC = 0.92, p < 0.0001 for mDCs; AUC = 0.82, p < 0.0001 for B lymphocytes) or infertility (AUC = 0.83, p < 0.0001 for mDCs; AUC = 0.73, p = 0.006 for B lymphocytes). Our findings suggest that the levels of TLR2-expressing cells, particularly mDCs and B lymphocytes, may be an effective biomarker of endometriosis, because the disease currently lacks clinically useful noninvasive biomarkers enabling early and cost-effective diagnosis.

scholarly journals Toll-like Receptor 2 as a Marker Molecule of Advanced Ovarian Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1205
Author(s):  
Małgorzata Sobstyl ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Rafał Hrynkiewicz ◽  
Dominika Bębnowska ◽  
Izabela Korona-Głowniak ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Screening Tests ◽  
Control Group ◽  
Newly Diagnosed ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Diagnostic Approaches ◽  
Toll Like Receptor 2 ◽  
Marker Molecule

Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.

scholarly journals Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dayu Pan ◽  
Yongjin Li ◽  
Fuhan Yang ◽  
Zenghui Lv ◽  
Shibo Zhu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Schwann Cell ◽  
Western Blot ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Cord Injury ◽  
Toll Like Receptor 2

Abstract Background Traumatic spinal cord injury (SCI) is a severely disabling disease that leads to loss of sensation, motor, and autonomic function. As exosomes have great potential in diagnosis, prognosis, and treatment of SCI because of their ability to easily cross the blood–brain barrier, the function of Schwann cell-derived exosomes (SCDEs) is still largely unknown. Methods A T10 spinal cord contusion was established in adult female mice. SCDEs were injected into the tail veins of mice three times a week for 4 weeks after the induction of SCI, and the control group was injected with PBS. High-resolution transmission electron microscope and western blot were used to characterize the SCDEs. Toll-like receptor 2 (TLR2) expression on astrocytes, chondroitin sulfate proteoglycans (CSPGs) deposition and neurological function recovery were measured in the spinal cord tissues of each group by immunofluorescence staining of TLR2, GFAP, CS56, 5-HT, and β-III-tublin, respectively. TLR2f/f mice were crossed to the GFAP-Cre strain to generate astrocyte specific TLR2 knockout mice (TLR2−/−). Finally, western blot analysis was used to determine the expression of signaling proteins and IKKβ inhibitor SC-514 was used to validate the involved signaling pathway. Results Here, we found that TLR2 increased significantly on astrocytes post-SCI. SCDEs treatment can promote functional recovery and induce the expression of TLR2 on astrocytes accompanied with decreased CSPGs deposition. The specific knockout of TLR2 on astrocytes abolished the decreasing CSPGs deposition and neurological functional recovery post-SCI. In addition, the signaling pathway of NF-κB/PI3K involved in the TLR2 activation was validated by western blot. Furthermore, IKKβ inhibitor SC-514 was also used to validate this signaling pathway. Conclusion Thus, our results uncovered that SCDEs can promote functional recovery of mice post-SCI by decreasing the CSPGs deposition via increasing the TLR2 expression on astrocytes through NF-κB/PI3K signaling pathway.

scholarly journals P1764EXPRESSION OF TOLL-LIKE RECEPTOR 4, BUT NOT THE TOLL-LIKE RECEPTOR 2, MAY BE USEFUL I ASSESING THE RISK OF RENAL TRANSPLANT DETERIORATION IN RECIPIENTS WHO HAVE RECOVERED FROM CYTOMEGALOVIRUS INFECTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sławomir Zmonarski ◽  
Mirosław Banasik ◽  
Tomasz Gołębiowski ◽  
Letachowicz Krzysztof ◽  
Joanna Zmonarska ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Cmv Infection ◽  
Toll Like Receptor 4 ◽  
Peripheral Blood Mononuclear ◽  
Data Binding ◽  
Toll Like Receptor 2 ◽  
The Impact

Abstract Background and Aims Data binding the expression of Toll-like (TLR) 4 receptor (TLR4ex), or TLR2 receptor (TLR2ex) and transplanted kidney (KT) function and symptomatic infections with CMV (CMV+) and are scarcely available. Objective: To investigate the relationships between TLR4ex and TLR2ex, a relapse of CMV+ and transplant function. Method Materials and methods: TLR4ex and TLR2ex were measured in peripheral blood mononuclear cells of KT recipients. We compared TLR4ex and TLR2ex among 25 CMV+ patients; 81 patients without CMV infection (CMVn). At the beginning (Day-0) TLR4ex, as well as concentrations of cyclosporin A (CyA) and tacrolimus (TAC) were determined. Both CMV+ and CMVn patients were divided according to the respective median of TLR4ex into groups of low-TLR2/4 expression (L-TLR2/4ex) and high-TLR2/4 expression (H-TLR2/4ex). Glomerular filtration rate (EGFR) was assessed on Day-0 and after the follow-up (F-up). The magnitudes of EGFR change (ΔEGFR) were evaluated. Stable treatment along the F-up period (median 11.9 months) was applied. Results Results. In CMV+ TLR2ex of 64,3% and TLR4ex in 67% is below respective median. Past CMV strongly affected TLR2ex and moderately TLR4ex. On Day-0: in CMV+ we found no link of TLR2 ex and TLR4ex with EGFR; In CMV+ TLR2ex and TLR4ex were lower but Day-0 EGFR did not differ from H-TLR2 or H-TLR4ex. In CMVn: GFR-TLR4ex link was present with no similar in case of GFR-TLR2ex. In patients treated with tacrolimus CMV strongly affected TLR4ex, blurring CMV+/CMVn differences. Post F-up: in CMV+ with L-TLR4ex EGFR declined, there was no change of EGFR in H-TLR4ex; L/H-TLR2ex showed no differences in EGFR. In CMVn with H-TLR4ex EGFR rose, there was no change in L-TLR4ex. In case of TLR2ex we showed no similar differences. Regression analysis points out the impact of CMV+ and TLR4ex on eGFR and ΔEGFR. No similar impact of CMV+ and TLR2ex on eEGFR and ΔEGFR was found. Conclusion Conclusion: In the group who had a symptomatic CMV + infection, low TLR4 expression increases the risk of worsening EGFR. In CMVn, high TLR4 expression increases the chance of EGFR improvement. Historic CMV + strongly affects TLR2ex. However, TLR2ex cannot be used as a factor in assessing the risk of EGFR deterioration.

scholarly journals Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus bacteremia

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nak-Hyun Kim ◽  
Ji Yeon Sung ◽  
Yoon Jung Choi ◽  
Su-Jin Choi ◽  
Soyeon Ahn ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Tertiary Care ◽  
High Sensitivity ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Staphylococcus Aureus Bacteremia ◽  
Tnf Α ◽  
Toll Like Receptor 2 ◽  
Cytokine Dysregulation

Abstract Background Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes. Methods Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6–9 d, 10–13 d, 14–19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA. Results TLR2 levels varied among 59 SAB patients. On days 2–5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2–5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007). Conclusion TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.

scholarly journals Involvement of Toll Like Receptor 2 Signaling in Secondary Injury during Experimental Diffuse Axonal Injury in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Yonglin Zhao ◽  
Junjie Zhao ◽  
Ming Zhang ◽  
Yahui Zhao ◽  
Jiaxi Li ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Internal Capsule ◽  
Secondary Injury ◽  
Pathophysiological Mechanism ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Mitogen Activated Protein ◽  
Toll Like Receptor 2

Treatment of diffuse axonal injury (DAI) remains challenging in clinical practice due to the unclear pathophysiological mechanism. Uncontrolled, excessive inflammation is one of the most recognized mechanisms that contribute to the secondary injury after DAI. Toll like receptor 2 (TLR2) is highlighted for the initiation of a vicious self-propagating inflammatory circle. However, the role and detailed mechanism of TLR2 in secondary injury is yet mostly unknown. In this study, we demonstrated the expression of TLR2 levels in cortex, corpus callosum, and internal capsule and the localization of TLR2 in neurons and glial cells in rat DAI models. Intracerebral knockdown of TLR2 significantly downregulated TLR2 expression, attenuated cortical apoptosis, lessened glial response, and reduced the secondary axonal and neuronal injury in the cortex by inhibiting phosphorylation of mitogen-activated protein kinases (MAPK) including Erk, JNK, and p38, translocation of NF-κB p65 from the cytoplasm to the nucleus, and decreasing levels of proinflammatory cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. On the contrary, administration of TLR2 agonist to DAI rats achieved an opposite effect. Collectively, we demonstrated that TLR2 was involved in mediating secondary injury after DAI by inducing inflammation via the MAPK and NF-κB pathways.

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