The effector EmcB is a deubiquitinase that inhibits RIG-I signaling.

Eukaryotes have cytosolic surveillance systems to detect invading microorganisms and initiate protective immune responses. In turn, host-adapted pathogens have evolved strategies to modulate these surveillance systems, which can promote dissemination and persistence in the host. The obligate intracellular pathogen infects mammalian hosts without activating many innate immune sensors.

Impedance-Based Phenotypic Readout of Transporter Function: A Case for Glutamate Transporters.

Excitatory amino acid transporters (EAAT/SLC1) mediate Na-dependent uptake of extracellular glutamate and are potential drug targets for neurological disorders. Conventional methods to assess glutamate transport are based on radiolabels, fluorescent dyes or electrophysiology, which potentially compromise the cell's physiology and are generally less suited for primary drug screens. Here, we describe a novel label-free method to assess human EAAT function in living cells, i.

Skin-resident innate lymphoid cells converge on a pathogenic effector state.

Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis.

Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity.

Mucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this complex equilibrium, here, we show that the enteric nervous system (ENS) plays an essential and non-redundant role in governing the antimicrobial protein (AMP) response. Using confocal microscopy and single-molecule fluorescence in situ mRNA hybridization (smFISH) studies, we observed that intestinal neurons produce the pleiotropic cytokine IL-18.

The translation of non-canonical open reading frames controls mucosal immunity.

The annotation of the mammalian protein-coding genome is incomplete. Arbitrary size restriction of open reading frames (ORFs) and the absolute requirement for a methionine codon as the sole initiator of translation have constrained the identification of potentially important transcripts with non-canonical protein-coding potential. Here, using unbiased transcriptomic approaches in macrophages that respond to bacterial infection, we show that ribosomes associate with a large number of RNAs that were previously annotated as 'non-protein coding'.

Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling.

Hepatitis C virus (HCV) infects 200 million people globally, and 60-80% of cases persist as a chronic infection that will progress to cirrhosis and liver cancer in 2-10% of patients. We recently demonstrated that HCV induces aberrant expression of two host microRNAs (miRNAs), miR-208b and miR-499a-5p, encoded by myosin genes in infected hepatocytes. These miRNAs, along with AU-rich-element-mediated decay, suppress IFNL2 and IFNL3, members of the type III interferon (IFN) gene family, to support viral persistence.

Interferon lambda 4 expression is suppressed by the host during viral infection.

Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon.

The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs.

IFNL3, which encodes interferon-λ3 (IFN-λ3), has received considerable attention in the hepatitis C virus (HCV) field, as many independent genome-wide association studies have identified a strong association between polymorphisms near IFNL3 and clearance of HCV. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) in the 3' untranslated region (UTR) of IFNL3 mRNA that dictated transcript stability.

IRF-5 and NF-κB p50 co-regulate IFN-β and IL-6 expression in TLR9-stimulated human plasmacytoid dendritic cells.

Synthetic oligonucleotides (ODN) expressing CpG motifs mimic the ability of bacterial DNA to trigger the innate immune system via TLR9. Plasmacytoid dendritic cells (pDCs) make a critical contribution to the ensuing immune response. This work examines the induction of antiviral (IFN-β) and pro-inflammatory (IL-6) cytokines by CpG-stimulated human pDCs and the human CAL-1 pDC cell line.

Systemic low-grade inflammation does not decrease skeletal muscle mass and protein synthesis in old rats.

Age-associated low-grade systemic inflammation may contribute to sarcopenia. We hypothesized that skeletal muscle mass and protein synthesis rate would be reduced in old rats exhibiting persistent low-grade inflammation compared to age-matched controls. Male 24-month-old Wistar rats exhibiting a low-grade systemic inflammation for at least one month (LGI group) were compared to non-inflamed rats (C group).

Substitution of casein by beta-casein or of whey protein isolate by alpha-lactalbumin does not affect mineral balance in growing rats.

Bovine milk protein fractions that enable modification of the protein composition and amino acid profile of infant formulas to mimic those of human milk have recently become available. To determine the effects on protein quality and mineral bioavailability of replacing casein by beta-casein and of whey protein isolate by alpha-lactalbumin, 4 groups of growing rats were fed for 3 wk diets containing 10% protein as 1) casein (control); 2) beta-casein; 3) casein:whey (40:60); or 4) beta-casein:alpha-lactalbumin (40:60). Protein quality, determined as protein efficiency ratio (PER), net protein utilization (NPU), biological value (BV) and protein digestibility (PD), as well as body weight gain, were higher (P < 0.

Free and protein-bound glutamine have identical splanchnic extraction in healthy human volunteers.

The objectives of the present study were to determine the splanchnic extraction of glutamine after ingestion of glutamine-rich protein ((15)N-labeled oat proteins) and to compare it with that of free glutamine and to determine de novo glutamine synthesis before and after glutamine consumption. Eight healthy adults were infused intravenously in the postabsorptive state with L-[1-(13)C]glutamine (3 micromol x kg(-1) x h(-1)) and L-[1-(13)C]lysine (1.5 micromol x kg(-1) x h(-1)) for 8 h.

Protein hydrolysate vs free amino acid-based diets on the nutritional recovery of the starved rat.

Background And Aims: To test the hypothesis that a peptide-based enteral product was equivalent to a low-fat, free amino acid-based formula in the nutritional and functional recovery of the starved rat.

Methods: Sixteen male Wistar rats were starved for 3 days. Then, rats were randomised to a whey protein hydrolysate-based diet or a free amino acid-based diet and refed for 3 days.

Neither glutamine nor arginine supplementation of diets increase glutamine body stores in healthy growing rats.

The aim of the work was to resolve whether glutamine and arginine supplemented diets affect plasma and tissue (muscle, liver and intestinal mucosa) glutamine concentrations, as well as glutaminase and glutamine synthetase specific activities. The trial was performed in growing rats fed 10% protein diets for 3 weeks. Protein sources were: whey proteins (W); whey proteins+free glutamine (WG); whey proteins+arginine (WA); and casein+wheat protein hydrolysate+acid whey (39:39:22), as source containing protein-bound glutamine (CGW).

Food deprivation and refeeding influence growth, nutrient retention and functional recovery of rats.

The objective of this work was to determine the effects of starvation and refeeding on growth, nutritional recovery and intestinal repair in starved rats. Male Wistar rats, weighing 200 g, were starved for 3 d, then refed a soy-based diet for another 3 d. Normally fed rats were given the same diet and used as controls.