Search results for "Toll"

TLR7 controls VSV replication in CD169(+) SCS macrophages and associated viral neuroinvasion

2019

Vesicular stomatitis virus (VSV) is an insect-transmitted rhabdovirus that is neurovirulent in mice. Upon peripheral VSV infection, CD169+ subcapsular sinus (SCS) macrophages capture VSV in the lymph, support viral replication, and prevent CNS neuroinvasion. To date, the precise mechanisms controlling VSV infection in SCS macrophages remain incompletely understood. Here, we show that Toll-like receptor-7 (TLR7), the main sensing receptor for VSV, is central in controlling lymph-borne VSV infection. Following VSV skin infection, TLR7−/− mice display significantly less VSV titers in the draining lymph nodes (dLN) and viral replication is attenuated in SCS macrophages. In contrast to effects o…

Are Toll-like receptors and decoy receptors involved in the immunopathogenesis of systemic lupus erythematosus and lupus-like syndromes?

2011

In this paper we focus our attention on the role of two families of receptors, Toll-like receptors (TLR) and decoy receptors (DcR) involved in the generation of systemic lupus erythematosus (SLE) and lupus-like syndromes in human and mouse models. To date, these molecules were described in several autoimmune disorders such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and SLE. Here, we summarize the findings of recent investigations on TLR and DcR and their role in the immunopathogenesis of the SLE.

On computation in statistical models with a psychophysical application

2004

FM Janne Kujalan tieteellisen laskennan väitöskirjan ”On computation in statistical models with a psychophysical application” (Laskennasta tilastollisissa malleissa psykofysiikkaan soveltaen) tarkastustilaisuus. Vastaväittäjänä FT Keijo Ruotsalainen (Oulun yliopisto) ja kustoksena professori Pekka Neittaanmäki.Kujala tehosti väitöskirjatutkimuksessaan tilastollisten ja fysikaalisten mallien laskentaa. Vaikka erinäisiin ongelmiin voidaan varsin helposti keksiä laskennallisia malleja, niiden käyttäminen ja vertailu on usein käytännössä mahdotonta tietokoneiden rajallisen tehon takia. Kujala etsi työssään vähemmän tehoa vaativia oikoteitä laskennallisten mallien käyttöön. Esimerkiksi kahden no…

Modelling phytoplankton in boreal lakes

2014

gllvm : Fast analysis of multivariate abundance data with generalized linear latent variable models in R

2019

1.There has been rapid development in tools for multivariate analysis based on fully specified statistical models or “joint models”. One approach attracting a lot of attention is generalized linear latent variable models (GLLVMs). However, software for fitting these models is typically slow and not practical for large datsets. 2.The R package gllvm offers relatively fast methods to fit GLLVMs via maximum likelihood, along with tools for model checking, visualization and inference. 3.The main advantage of the package over other implementations is speed e.g. being two orders of magnitude faster, and capable of handling thousands of response variables. These advances come from using variationa…

Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps

2013

Background A number of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) are resistant to oral corticosteroids. Mucin 1 (MUC1) shows anti-inflammatory properties, and its cytoplasmic tail (CT) interacts with transcription factors, facilitating their nuclear translocation. Because glucocorticoid receptor (GR) nuclear translocation is key to the anti-inflammatory effect of corticosteroids, we hypothesized that MUC1 is involved in the effectiveness of corticosteroids. Objective To analyze the role of MUC1 in corticosteroid effectiveness in different cohorts of patients with CRSwNP and elucidate the possible mechanisms involved. Methods Seventy-three patients with CRSwNP took oral…

Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension

2013

Aims Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key component of the innate immune system, which is activated by exogenous and endogenous ligands. Hypertension is associated with end-organ damage and thus might lead to the release of damage-associated molecular patterns (DAMPs), which are endogenous activators of TLR4 receptors. The present study aimed to elucidate whether TLR4 signalling is able to modulate vascular contractility in …

Human antiphospholipid antibodies induce TNFα in monocytes via Toll-like receptor 8

2009

The antiphospholipid syndrome (APS) is characterized by recurrent arterial and/or venous thromboses, pregnancy loss and the presence of antiphospholipid antibodies (aPL). One of the discussed mechanisms of this thrombotic activity in APS patients is attributed to TNFalpha secretion in monocytes after aPL stimulation. To investigate this mechanism in detail, we employed a monoclonal aPL and IgG fractions of APS patients for stimulation of human peripheral monocytes. Stimulation with this monoclonal aPL resulted in an increased expression and secretion of TNFalpha, caused by specific upregulation of TLR8 mRNA and protein expression levels. To confirm the specificity of this finding we could d…

Monophosphoryl lipid A coating of hydroxyethyl starch nanocapsules drastically increases uptake and maturation by dendritic cells while minimizing th…

2015

Enhancing delivery of antigens to dendritic cells (DCs) is essential for the induction of vigorous antigen-specific cellular immune responses. Aim of the present study was to evaluate the properties of hydroxyethyl starch nanocapsules (HES-NCs) functionalized with anti-CD40, anti-DEC205, interferon-γ (IFNγ) and/or monophosphoryl lipid A (MPLA) with respect to the overall uptake, the released cytokine profile, and the influence on phenotypic maturation of human monocyte-derived DCs using flow cytometry, confocal microscopy and enzyme-linked immunosorbent assays. NC uptake by DCs was significantly enhanced by functionalizing NCs with anti-CD40 or MPLA. With respect to the cytokine profile and…

Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis.

2015

Dendritic cells (DCs) are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function in vivo remain largely unknown. The beta-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of beta-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA). Deletion of beta-catenin specifically in DCs was achieved by crossing conditional knockout mice with a CD11c-Cre transgenic mouse line. Bone marrow-derived DCs (BMDCs) were generated and used to study the maturation profile of …