Silver nanoparticles impair retinoic acid-inducible gene I mediated mitochondrial anti-viral immunity by blocking the autophagic flux in lung epithelial cells

Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as alternative to antivirals to treat human infectious diseases, especially Influenza virus infection where antivirals have generally proven unsuccessful. However, concerns about the use of AgNPs on humans arise from their potential toxicity, although mechanisms are not well-understood. We show here, in the context of Influenza virus infection of lung epithelial cells, that AgNPs down-regulated Influenza induced-CCL-5 and -IFN-β release (two cytokines important in anti-viral immunity) through RIG-I inhibition, while enhancing IL-8 production, a cytokine important for mobilizing host antibacterial responses. AgNPs activity was independent of coating and was not observed with gold nanoparticles. Down-stream analysis indicated that AgNPs disorganized the mitochondrial network and prevented the anti-viral IRF-7 transcription factor influx into the nucleus. Importantly, we showed that the modulation of RIG-I-IRF-7 pathway was concomitant with inhibition of either classical or alternative autophagy (ATG-5- and Rab-9 dependent, respectively), depending on the epithelial cell type used. Altogether, this demonstration of a AgNPs-mediated functional dichotomy (down-regulation of IFN-dependent anti-viral responses and up-regulation of IL-8 -dependent antibacterial responses) may have practical implications for their use in the clinic

New star-shaped molecules derived from thieno[3,2-b]thiophene unit and triphenylamine

International audienc

5-Ureido-3,3-diphenyl-3H-naphtho[2,1-b]pyrans: Photoswitchable self-assembling architectures

5-Ureido-3,3-diphenyl-3H-naphtho[2,1-b]pyrans have been synthesized and their photochromic properties have been quantified using UV-Visible spectroscopy. The urea pattern is responsive for the selfassembling properties under both colourless and coloured forms whereas the corresponding amino derivatives do not show any aggregative properties. The geometries of the different states have been assigned using 1H and 19F NMR spectroscopies, and thereafter their respective kind of aggregates could be proposed through the different inter- and intramolecular interactions. Upon UV irradiation, the pyranic ring is opened and the resulting photogenerated carbonyl group is competing with the urea in the self-assembling process and consequently strongly affects the supramolecular assemblies. The inter- and intramolecular contributions have been quantified through 1D and 2D NMR experiments along with the variation in the concentration

A star-shaped molecule as hole transporting material in solution-processed thin-film transistors

The semiconductor potentialities of a new star-shaped molecule consisting of a triphenylamine core carrying π-conjugated thiophene and thieno[3,2-b]-thiophene-C9H19 units, VM5C9, has been evaluated by its implementation as active layer in organic thin-film transistors (OTFTs). The photophysical properties of VM5C9 were previously studied by UV–vis absorption and emission spectroscopy in both dilute solutions and thin films. The latter were prepared from solutions in toluene, chloroform (CHCl3), dichloromethane (CH2Cl2) and tetrahydrofuran (THF) by spin-coating on substrates following by an annealing to a controlled temperature ranging from 60 °C to 90 °C. Thin-film morphology and structure were characterized by X-ray diffraction and scanning electron microscopy. Solution processed thin films lead to glassy films. An optimized hole mobility up to 3.8 × 10−4 cm2/V s could be reached by a fine control of the liquid-phase deposition method, the choice of solvent and post-annealing temperature

Systèmes Thienylène-Phénylène sous l'œil du physico-chimiste. Apport du couplage SPE-UV/Quantochimie.

Il existe de nombreuses familles d'oligomères Π-conjugués, telles que celles des oligothiophènes et des oligophénylènes, qui représentent une classe importante de semi-conducteurs. [1] Les propriétés électroniques et optiques sont liées à la fois à la nature des motifs conjugués et également à la longueur de la conjugaison. Plusieurs questions importantes se posent : comment déterminer puis prévoir leurs propriétés, quantifier expérimentalement les interactions inter-cycles, aller plus loin dans la description de ces modèles ? Nous montrerons que l'apport de la physico-chimie s'avère ici intéressant et qu'en particulier la spectroscopie photoélectronique à rayonnement UV, en phase gazeuse, peut être un outil puissant afin de mettre en évidence et quantifier la « magnitude » des interactions Πphényle-Πthiophène. [2] Couplé à la quantochimie, ce « tandem » permet d'aller encore plus loin dans l'étude de ces systèmes, notamment en précisant la nature et l'allure des orbitales intervenant dans la délocalisation mais également en décrivant la nature des interactions favorisant la quasi-planéité de ces systèmes : interactions électrostatique, électronique ... ? Ainsi vous pourrez d'une part comprendre quel rôle jouent les substituants au niveau de la structure géométrique de ces composés et d'autre part « visualiser » expérimentalement leur implication dans la délocalisation. [1] a) S. Hotta, S. A. Lee, Synth. Met. 1999, 101, 551; b) S. Hotta, S. A. Lee, T. Tamaki J. Heterocyclic Chem. 2000, 37, 25; c) S. Hotta, S. A. Lee, H. Kimura J. Heterocyclic Chem. 2000, 37, 25. [2] S. Lois, J.-Ch. Florès, J.-P. Lère-Porte, F. Serein-Spirau, J.E.Moreau, K. Miqueu, J.-M. Sotiropoulos, P. Baylère, M. Tillard, C. Belin Eur. Org. Chem. sous press

Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis

Cystic fibrosis (CF) is caused by defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. Morbidity is mainly due to early airway infection. We hypothesized that S. aureus clearance during the first hours of infection was impaired in CF human Airway Surface Liquid (ASL) because of a lowered pH. The ASL pH of human bronchial epithelial cell lines and primary respiratory cells from healthy controls (WT) and patients with CF was measured with a pH microelectrode. The antimicrobial capacity of airway cells was studied after S. aureus apical infection by counting surviving bacteria. ASL was significantly more acidic in CF than in WT respiratory cells. This was consistent with a defect in bicarbonate secretion involving CFTR and SLC26A4 (pendrin) and a persistent proton secretion by ATP12A. ASL demonstrated a defect in S. aureus clearance which was improved by pH normalization. Pendrin inhibition in WT airways recapitulated the CF airway defect and increased S. aureus proliferation. ATP12A inhibition by ouabain decreased bacterial proliferation. Antimicrobial peptides LL-37 and hBD1 demonstrated a pH-dependent activity. Normalizing ASL pH might improve innate airway defense in newborns with CF during onset of S. aureus infection. Pendrin activation and ATP12A inhibition could represent novel therapeutic strategies to normalize pH in CF airways

Author Correction: Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis (Scientific Reports, (2019), 9, 1, (6516), 10.1038/s41598-019-42751-4)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation

Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCPs). How ILCPs give rise to mature tissue-resident ILCs remains unclear. Here, we identify circulating and tissue ILCPs in humans that fail to express the transcription factors and cytokine outputs of mature ILCs but have these signature loci in an epigenetically poised configuration. Human ILCPs robustly generate all ILC subsets in vitro and in vivo. While human ILCPs express low levels of retinoic acid receptor (RAR)-related orphan receptor C (RORC) transcripts, these cells are found in RORC-deficient patients and retain potential for EOMES+ natural killer (NK) cells, interferon gamma-positive (IFN-γ+) ILC1s, interleukin (IL)-13+ ILC2s, and for IL-22+, but not for IL-17A+ ILC3s. Our results support a model of tissue ILC differentiation ("ILC-poiesis"), whereby diverse ILC subsets are generated in situ from systemically distributed ILCPs in response to local environmental signals

WAPing out pathogens and disease in the mucosa: roles for SLPI and Trappin-2

The interface between the external environment and the body’s internal structures is defined by the mucosal tissue and the viscous lining fluid that is responsible for maintaining its integrity and protecting internal structures from damage or infection. Human mucosal fluids include seminal fluid, cervical mucus, bronchial and nasal secretions and tears whose composition is particularly complicated. This review will focus on just two related molecules that are present in the mucosal lining fluid, namely, trappin-2 and secretory leucocyte protease inhibitor (SLPI), that are responsible for many of the homeostatic and host defence functions of these uniquely situated viscous sols. This review will focus on our increasing understanding of these two molecules from a simple role as local antibiotics that respond to pathogen invasion to major orchestrators of cellular interplays, host defence mechanisms and immune homeostasis