Ebola Virus Infection of Flt3-Dependent, Conventional Dendritic Cells and Antigen Cross-presentation Leads to High Levels of T-Cell Activation.

Background: Previous studies have described that Ebola virus (EBOV) infection of human monocyte-derived dendritic cells (moDCs) inhibits dendritic cell (DC) maturation, resulting in poor T-cell activation. However, it is unknown how other DC subsets distinct from moDCs respond to EBOV infection.

Methods: To better understand how DCs initiate T-cell activation during EBOV infection, we assessed the response of conventional mouse DCs (cDCs) to EBOV infection utilizing a recombinant EBOV expressing the model antigen ovalbumin.

Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling.

Background: Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer's disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown.

Results: Here, we provide the prime evidence that titanium dioxide (TiO) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrP), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD.

Inactivation Methods for Experimental Nipah Virus Infection.

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of available vaccines and therapeutics, NiV needs to be handled in biosafety level 4 (BSL-4) laboratories. Safe inactivation of samples containing NiV is thus necessary to allow further processing in lower containment areas.

Roadbumps at the Crossroads of Integrating Behavioral and Approaches for Neurotoxicity Assessment.

With the appreciation that behavior represents the integration and complexity of the nervous system, neurobehavioral phenotyping and assessment has seen a renaissance over the last couple of decades, resulting in a robust database on rodent performance within various testing paradigms, possible associations with human disorders, and therapeutic interventions. The interchange of data across behavior and other test modalities and multiple model systems has advanced our understanding of fundamental biology and mechanisms associated with normal functions and alterations in the nervous system. While there is a demonstrated value and power of neurobehavioral assessments for examining alterations due to genetic manipulations, maternal factors, early development environment, the applied use of behavior to assess environmental neurotoxicity continues to come under question as to whether behavior represents a sensitive endpoint for assessment.

The Challenges of 21st Century Neurotoxicology: The Case of Neurotoxicology Applied to Nanomaterials.

After a short background discussing engineered nanomaterials (ENMs) and their physicochemical properties and applications, the present perspective paper highlights the main specific points that need to be considered when examining the question of neurotoxicity of nanomaterials. It underlines the necessity to integrate parameters, specific tools, and tests from multiple sources that make neurotoxicology when applied to nanomaterials particularly complex. Bringing together the knowledge of multiple disciplines e.

Prenatal exposure to paraquat and nanoscaled TiO aerosols alters the gene expression of the developing brain.

Nanopesticides are innovative pesticides involving engineered nanomaterials in their formulation to increase the efficiency of plant protection products, while mitigating their environmental impact. Despite the predicted growth of the nanopesticide use, no data is available on their inhalation toxicity and the potential cocktail effects between their components. In particular, the neurodevelopmental toxicity caused by prenatal exposures might have long lasting consequences.

Metagenomic Snapshots of Viral Components in Guinean Bats.

To prevent the emergence of zoonotic infectious diseases and reduce their epidemic potential, we need to understand their origins in nature. Bats in the order Chiroptera are widely distributed worldwide and are natural reservoirs of prominent zoonotic viruses, including Nipah virus, Marburg virus, and possibly SARS-CoV-2. In this study, we applied unbiased metagenomic and metatranscriptomic approaches to decipher the virosphere of frugivorous and insectivorous bat species captured in Guéckédou, Guinea, the epicenter of the West African Ebola virus disease epidemic in 2013-2016.

Melanoma-associated fibroblasts impair CD8+ T cell function and modify expression of immune checkpoint regulators via increased arginase activity.

This study shows that melanoma-associated fibroblasts (MAFs) suppress cytotoxic T lymphocyte (CTL) activity and reveals a pivotal role played by arginase in this phenomenon. MAFs and normal dermal fibroblasts (DFs) were isolated from surgically resected melanomas and identified as Melan-A-/gp100-/FAP+ cells. CTLs of healthy blood donors were activated in the presence of MAF- and DF-conditioned media (CM).

Chronic Oral Exposure to Synthetic Amorphous Silica (NM-200) Results in Renal and Liver Lesions in Mice.

Introduction: Silicon dioxide, produced as synthetic amorphous silica (SAS), is made of nanoparticles (NPs), either present as such or as agglomerates and aggregates, and is widely used in many types of food processes and products as an additive. To assess whether repeated, long-term exposure to SAS NPs may result in adverse effects, mice were exposed for 18 months drinking water to NM-200, one of the reference nanostructured silica used for applications related to food, at 4.8 mg NM-200/kg body weight per day, a dose relevant to the estimated dietary exposure to SAS in humans.

Skin-homing CD8 T cells preferentially express GPI-anchored peptidase inhibitor 16, an inhibitor of cathepsin K.

This study sought to identify novel CD8 T cell homing markers by studying acute graft versus host disease (aGvHD), typically involving increased T cell homing to the skin and gut. FACS-sorted skin-homing (CD8β /CLA ), gut-homing (CD8β /integrinβ7 ), and reference (CD8β /CLA /integrinβ7 ) T cells were compared in patients affected by cutaneous and/or gastrointestinal aGVHD. Microarray analysis, qPCR, and flow cytometry revealed increased expression of peptidase inhibitor 16 (PI16) in skin-homing CD8 T cells.

Nano- and neurotoxicology: An emerging discipline.

The present critical review analyzes the question of how nanoparticles from continuously growing industrial production and use of nanomaterials may impact human brain health. Available evidence suggests incomplete effectiveness of protective barriers of the brain against nanoparticles translocation to the brain. This raises concerns of potential effects of manufactured nanoparticles on brain functions, given that nanoparticle's potential to induce oxidative stress, inflammation, death by apoptosis, or changes in the level of expression of certain neurotransmitters.

Oral Exposure to Paraquat Triggers Earlier Expression of Phosphorylated α-Synuclein in the Enteric Nervous System of A53T Mutant Human α-Synuclein Transgenic Mice.

The misfolded α-synuclein protein, phosphorylated at serine 129 (pSer129 α-syn), is the hallmark of Parkinson disease (PD). Detected also in the enteric nervous system (ENS), it supports the recent theory that PD could start in the gut, rather than the brain. In a previous study, using a transgenic mouse model of human synucleinopathies expressing the A53T mutant α-synuclein (TgM83), in which a neurodegenerative process associated with α-synuclein occurs spontaneously in the brain, we have shown earlier onset of pSer129 α-syn in the ENS.

Unique patterns of CD8+ T-cell-mediated organ damage in the Act-mOVA/OT-I model of acute graft-versus-host disease.

T-cell receptor (TCR)-transgenic models of acute graft-versus-host disease (aGvHD) offer a straightforward and highly controlled approach to study the mechanisms and consequences of T-cell activation following allogeneic hematopoietic stem cell transplantation (aHSCT). Here, we report that aHSCT involving OT-I mice as donors, carrying an ovalbumin-specific CD8+ TCR, and Act-mOVA mice as recipients, expressing membrane-bound ovalbumin driven by the β-actin promoter, induces lethal aGvHD in a CD8+ T-cell-dependent, highly reproducible manner, within 4-7 days. Tracking of UBC-GFP/OT-I graft CD8+ T cells disclosed heavy infiltration of the gastrointestinal tract, liver, and lungs at the onset of the disease, and histology confirmed hallmark features of gastrointestinal aGVHD, hepatic aGvHD, and aGvHD-associated lymphocytic bronchitis in infiltrated organs.

Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells contributes to generation of regulatory T cells.

The role of complement in the regulation of T cell immunity has been highlighted recently by several groups. We were prompted to reinvestigate the role of complement receptor type 1 (CR1, CD35) [corrected] in human T cells based on our earlier data showing that activated human T cells produce C3 (Torok et al. (2012) [48]) and also by results demonstrating that engagement of Membrane Cofactor Protein (MCP, CD46) induces a switch of anti-CD35-activated [corrected] helper T cells into regulatory T cells (Kemper et al.

Early and persistent expression of phosphorylated α-synuclein in the enteric nervous system of A53T mutant human α-synuclein transgenic mice.

Alpha-synuclein is a key protein in Parkinson disease (PD) and dementia with Lewy bodies. It is found in Lewy bodies in the brains of PD patients and has been reported in the peripheral nervous system in postmortem tissues from PD patients and in biopsies from patients in the preclinical phase of PD. Here, we used a transgenic mouse model of human synucleinopathies expressing the A53T mutant α-synuclein (TgM83) in which a neurodegenerative process associated with α-synuclein occurs spontaneously and increases with age.

Concerns regarding nanosized titanium dioxide nasal exposure and neurotoxicity study by Ze et al.

Scientific articles dealing with nanotoxicology are particularly awaited and important, as in the field of nanotechnology, a relatively new domain; they likely have a significant impact not only on our perception of the risk and danger potentially associated with nanomaterials but also on regulatory decisions with regard to their use in consumer products. Because nanotoxicology refers to the work of researchers from different domains of expertise, it appears also more difficult to secure accurate review and thus accurate conclusions. In that context, particular attention must be drawn on these studies.

[Is the brain protected from the impact of nanomaterial exposure?].

Beside natural and entropic nanoparticules (NPs), the engineered nanoparticules are now more and more present in many different industrial and medical applications. Notably, despite this fast development of the nanotechnologies, little is known about a possible impact on health and environment. Above all, the impact on human body and especially on the brain is not known.

L-type bovine spongiform encephalopathy in genetically susceptible and resistant sheep: changes in prion strain or phenotypic plasticity of the disease-associated prion protein?

Background: Sheep with prion protein (PrP) gene polymorphisms QQ171 and RQ171 were shown to be susceptible to the prion causing L-type bovine spongiform encephalopathy (L-BSE), although RQ171 sheep specifically propagated a distinctive prion molecular phenotype in their brains, characterized by a high molecular mass protease-resistant PrP fragment (HMM PrPres), distinct from L-BSE in QQ171 sheep.

Methods: The resulting infectious and biological properties of QQ171 and RQ171 ovine L-BSE prions were investigated in transgenic mice expressing either bovine or ovine PrP.

Results: In both mouse lines, ovine L-BSE transmitted similarly to cattle-derived L-BSE, with respect to survival periods, histopathology, and biochemical features of PrPres in the brain, as well as splenotropism, clearly differing from ovine classic BSE or from scrapie strain CH1641.

Unique properties of the classical bovine spongiform encephalopathy strain and its emergence from H-type bovine spongiform encephalopathy substantiated by VM transmission studies.

In addition to classical bovine spongiform encephalopathy (C-BSE), which is recognized as being at the origin of the human variant form of Creutzfeldt-Jakob disease, 2 rare phenotypes of BSE (H-type BSE [H-BSE] and L-type BSE [L-BSE]) were identified in 2004. H-type BSE and L-BSE are considered to be sporadic forms of prion disease in cattle because they differ from C-BSE with respect to incubation period, vacuolar pathology in the brain, and biochemical properties of the protease-resistant prion protein (PrP) in natural hosts and in some mouse models that have been tested. Recently, we showed that H-BSE transmitted to C57Bl/6 mice resulted in a dissociation of the phenotypic features, that is, some mice showed an H-BSE phenotype, whereas others had a C-BSE phenotype.

Differentiation of prions from L-type BSE versus sporadic Creutzfeldt-Jakob disease.

We compared transmission characteristics for prions from L-type bovine spongiform encephalopathy and MM2-cortical sporadic Creutzfeldt-Jakob disease in the Syrian golden hamster and an ovine prion protein-transgenic mouse line and isolated distinct prion strains. Our findings suggest the absence of a causal relationship between these diseases, but further investigation is warranted.

Selection of distinct strain phenotypes in mice infected by ovine natural scrapie isolates similar to CH1641 experimental scrapie.

A few cases of transmissible spongiform encephalopathies in sheep have been described in France in which the protease-resistant prion protein (PrP(res)) exhibited some features in Western blot of experimental bovine spongiform encephalopathy in sheep. Their molecular characteristics were indistinguishable from those produced in the CH1641 experimental scrapie isolate. Four of these CH1641-like isolates were inoculated intracerebrally into wild-type C57Bl/6 mice.

Stem cell therapy extends incubation and survival time in prion-infected mice in a time window-dependant manner.

Prion diseases, which are mostly represented in humans by Creutzfeldt-Jakob disease, are transmissible neurodegenerative disorders characterized by vacuolization and neuronal loss, as well as by the accumulation of an abnormal form of the prion protein. These disorders have yet no effective treatment, and drugs that block prion replication in vitro do not significantly slow down the progression of the disease when used in vivo at late stages. Cell therapy that has been already tested in other neurodegenerative disorders therefore represents an interesting alternative approach.