Understanding the Innate Immune Response in Viral Hepatitis : Interferons and NK Cells

HBV and HCV infection are the two leading causes of chronic liver inflammation worldwide, affecting an approximate 370–390 million people. Currently, th

Understanding IFNλ in rheumatoid arthritis

Unraveling the mechanisms underlying the inflammatory response in rheumatoid arthritis is crucial in order to better understand the disease and to develop novel therapeutic approaches. Although the effect of type I interferons on fibroblasts and in the context of rheumatoid arthritis has been described for some time, little is known on the effects of the type III interferons, also known as IFNλ. In a previous issue, Xu and colleagues demonstrate that one of the members of the IFNλ family, IFNλ1, enhances Toll-like receptor expression and consequently promotes the production of proinflammatory cytokines known to be involved in initiating and maintaining the inflammatory responses in rheumatoid arthritis

Volatilization of tri-allate, ethoprophos and parathion measured with four methods after spraying on a sandy soil

At about eleven times after application of tri-allate, ethoprophos and parathion to a sandy soil, their rates of volatilization were determined by the aerodynamic method (AD), the Bowen-ratio method (BR), the theoretical-profile method (TP) and the Box method. The volatilization was highest for tri-allate and lowest for parathion. On the first day after application, the volatilization rate decreased sharply, but thereafter the decrease was more gradual. The differences in volatilization rate as determined with the AD, BR and TP methods were comparatively small. The rates determined with the Box method were mostly lower than those determined with the other methods

Overwaaien van bestrijdingsmiddelen naar waterlopen bij bespuiting in de bloembollenteelt

Het overwaaien van bestrijdingsmiddelen bij bespuitingen in de bloembollenteelt, als mogelijke bron van verontreiniging van waterlopen, is onderzocht. De methoden voor het meten van de depositie van de voorbeeldstoffen esfenvaleraat, chloridazon en Brilliant Sulfoflavine op verschillende collectoren zijn getoetst. In de drie veldproeven nam de aërieke depositie buiten het gewas af tot respectievelijk 0,6%, 0,9% en 2,1% van de dosering op de benedenwindse slootrand (op 3 u 4 m afstand). De aërieke depositie op het wateroppervlak (op ongeveer 5 m afstand) lag rond 0,5% van de dosering. Een spuitvrije zone van 4 u 5 m breedte levert een grote bijdrage aan het verminderen van overwaaien van spuitvloeistof naar de waterlopen

Volatilization of parathion and chlorothalonil after spraying onto a potato crop

At fourteen times after application of parathion and chlorothalonil to a potato crop their rates of volatilization were determined by the aerodynamic and Bowen ratio methods. The highest volatilization rate of parathion occurred shortly after application. In the first hours after application its volatilization rate decreased sharply; thereafter it decreased more gradually. The volatilization rate of chlorothalonil at one week after application did not differ much from that shortly after application. Weather conditions in the first twenty-four hours after application of both pesticides were simulated in a chamber. The volatilization of parathion in the chamber had the same order of magnitude as that determined in the field

NK cell phenotypic and functional shifts coincide with specific clinical phases in the natural history of chronic HBV infection

Background Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection. Methods Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells. Results The overall composition, phenotype, and cytolytic activity of the NK cells remained constant across all clinical phases, with the exception of a few specific markers (KIRs, NKp46). CD56bright NK cells of chronic HBV patients differed in their ability to produce IFN-γ between the clinical phases pre- and post-HBeAg seroconversion. Conclusion This depicts a shift in NK cell characteristics between the immune active, under heavy viral or immune pressure, and inactive carrier phases, that coincides

NK cells in self-limited HCV infection exhibit a more extensively differentiated, but not memory-like, repertoire

Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings. By making use of a unique cohort of monitored, at-risk intravenous drug users in this study, we were able to dissect the phenotypic and functional parameters associated with NK cell differentiation and NK cell memory in patients 3 years after acute HCV infection and either the subsequent self-clearance or progression to chronicity. We observed increased expression of cytolytic mediators and markers CD56bright and NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection. Patients with a self-limited infection expressed higher levels of differentiation-associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively differentiated NK cell phenotype is associated with self-clearance in HCV patients, while the NK cells of chronic patients exhibited more naïve and effector NK cell phenotypic and functional characteristics. The identification of these distinct NK cell repertoires may shed light on the role NK cells play in determining the outcome of acute HCV infections, and the underlying immunological defects that lead to chronicity

Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees

In humans, clearance of hepatitis C virus (HCV) infection is associated with genetic variation near the IL-28B gene and the induction of interferon-stimulated genes, like IP-10. Also in chimpanzees spontaneous clearance of HCV is observed. To study whether similar correlations exist in these animals, a direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients was performed. All chimpanzees studied were monomorphic for the human IL-28B SNPs which are associated with spontaneous and treatment induced HCV clearance in humans. As a result, these particular SNPs cannot be used for clinical association studies in chimpanzees. Although these human SNPs were absent in chimpanzees, gene variation in this region was present however, no correlation was observed between different SNP-genotypes and HCV outcome. Strikingly, IP-10 levels in chimpanzees correlated with HCV-RNA load and γGT, while such correlations were not observed in humans. The correlation between IP-10, γGT and virus load in chimpanzees was not found in patients and may be due to the lack of lifestyle-related confounding factors in chimpanzees. Direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients in relation to HCV infection, illustrates that the IFN-pathways are important during HCV infection in both species. The Genbank EMBL accession numbers assigned to chimpanzees specific sequences near the IL-28B gene are HE599784 and HE599785

Chemotherapy for pulmonary large cell neuroendocrine carcinomas: Does the regimen matter?

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