Search results for "Toll-like receptor"

Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches.

2017

Diabetic microangiopathy, including retinopathy, is characterized by abnormal growth and leakage of small blood vessels, resulting in local edema and functional impairment of the depending tissues. Mechanisms leading to the impairment of microcirculation in diabetes are multiple and still largely unclear. However, a dysregulated vascular regeneration appears to play a key role. In addition, oxidative and hyperosmolar stress, as well as the activation of inflammatory pathways triggered by advanced glycation end-products and toll-like receptors, have been recognized as key underlying events. Here, we review recent knowledge on cellular and molecular pathways of microvascular disease in diabet…

Adipocytes as a Link Between Gut Microbiota-Derived Flagellin and Hepatocyte Fat Accumulation

2016

While the role of both elevated levels of circulating bacterial cell wall components and adipose tissue in hepatic fat accumulation has been recognized, it has not been considered that the bacterial components-recognizing adipose tissue receptors contribute to the hepatic fat content. In this study we found that the expression of adipose tissue bacterial flagellin (FLG)-recognizing Toll-like receptor (TLR) 5 associated with liver fat content (r = 0.699, p = 0.003) and insulin sensitivity (r = -0.529, p = 0.016) in humans (n = 23). No such associations were found for lipopolysaccharides (LPS)-recognizing TLR4. To study the underlying molecular mechanisms of these associations, human HepG2 he…

TLR3-independent activation of mast cells by cytomegalovirus contributes to control of pulmonary infection.

2017

Interstitial pneumonia is a life-threatening clinical manifestation of human cytomegalovirus (hCMV) infection. In particular, it can be deadly in patients with hematopoietic malignancies who undergo hematopoietic cell transplantation (HCT) in whom a ‘window of risk’, which is defined by transient immunodeficiency, occurs between hematoablative therapeutic treatment and immunological reconstitution. As few clinical studies have addressed the underlying mechanisms for this phenomenon, a mouse model of HCT and murine cytomegalovirus (mCMV) infection has been established and has revealed a key role for antiviral CD8+ T cells in controlling pulmonary infections. Using this mouse model, recent st…

TLR4 participates in the transmission of ethanol-induced neuroinflammation via astrocyte-derived extracellular vesicles

2019

Background Current evidence indicates that extracellular vesicles (EVs) participate in intercellular signaling, and in the regulation and amplification of neuroinflammation. We have previously shown that ethanol activates glial cells through Toll-like receptor 4 (TLR4) by triggering neuroinflammation. Here, we evaluate if ethanol and the TLR4 response change the release and inflammatory content of astrocyte-derived EVs, and whether these vesicles are capable of communicating with neurons by spreading neuroinflammation. Methods Cortical neurons and astrocytes in culture were used. EVs were isolated from the extracellular medium of the primary culture of the WT and TLR4-KO astrocytes treated …

Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins.

2019

Background & Aims Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial. Methods C57BL/6 (control), Myd88–/–, Ticam1–/–, and Il15–/– mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and int…

Allergen-Specific Low Zone Tolerance Is Independent of MRP8/14-, TLR4-, TLR7-, and TLR9-Mediated Immune Processes.

2017

Screening of herbal extracts for TLR2- and TLR4-dependent anti-inflammatory effects.

2018

Herbal extracts represent an ample source of natural compounds, with potential to be used in improving human health. There is a growing interest in using natural extracts as possible new treatment strategies for inflammatory diseases. We therefore aimed at identifying herbal extracts that affect inflammatory signaling pathways through toll-like receptors (TLRs), TLR2 and TLR4. Ninety-nine ethanolic extracts were screened in THP-1 monocytes and HeLa-TLR4 transfected reporter cells for their effects on stimulated TLR2 and TLR4 signaling pathways. The 28 identified anti-inflammatory extracts were tested in comparative assays of stimulated HEK-TLR2 and HEK-TLR4 transfected reporter cells to dif…

Role of Toll-like receptors in systemic Candida albicans infections.

2009

Toll-like receptors (TLRs) constitute a family of pattern-recognition receptors (PRRs) that recognize molecular signatures of microbial pathogens and function as sensors for infection that induce the activation of the innate immune responses as well as the subsequent development of adaptive immune responses. It is well established that TLRs, mainly TLR2 and TLR4, are involved in the host interaction with Candida albicans and play a significant role in the development of host immune responses during candidiasis. Recognition of C. albicans by TLRs on the phagocytic cells activates intracellular signaling pathways that trigger production of proinflammatory cytokines that are critical for innat…

Ceftaroline modulates the innate immune and host defense responses of immunocompetent cells exposed to cigarette smoke.

2017

Abstract Background Cigarette smoke, the principal risk factor for chronic obstructive pulmonary disease (COPD), negatively influences the effectiveness of the immune system’s response to a pathogen. The antibiotic ceftaroline exerts immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke. Aims and methods The present study aims to assess the effects of ceftaroline on TLR2 and TLR4 expression, LPS binding and TNF-α and human beta defensin (HBD2) release in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-α and HBD2 release w…

Gut Microbiota Restricts NETosis in Acute Mesenteric Ischemia-Reperfusion Injury.

2020

Objective: Recruitment of neutrophils and formation of neutrophil extracellular traps (NETs) contribute to lethality in acute mesenteric infarction. To study the impact of the gut microbiota in acute mesenteric infarction, we used gnotobiotic mouse models to investigate whether gut commensals prime the reactivity of neutrophils towards formation of neutrophil extracellular traps (NETosis). Approach and Results: We applied a mesenteric ischemia-reperfusion (I/R) injury model to germ-free (GF) and colonized C57BL/6J mice. By intravital imaging, we quantified leukocyte adherence and NET formation in I/R-injured mesenteric venules. Colonization with gut microbiota or monocolonization with Esch…