Search results for "Immune system"
showing 10 items of 2885 documents
Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth
2012
International audience; Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the relea…
The sharedneoantigen landscape of MSI cancers reflects immunoediting during tumor evolution
2019
AbstractThe immune system can recognize and attack cancer cells, especially those with a high load of mutation-inducedneoantigens. Suchneoantigens are particularly abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and toneoantigen-inducing translational frameshifts. The abundance of mutationalneoantigens renders MSI cancers sensitive to immune checkpoint blockade. However, the neoantigen landscape of MMR-deficient cancers has not yet been systematically mapped. In the present study, we used a novel tool to monitorneoantigen-inducing indel mutations in MSI colore…
Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic…
2018
ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in m…
Mucin induces CRISPR-Cas defence in an opportunistic pathogen
2021
AbstractParasitism by bacteriophages has led to the evolution of a variety of defense mechanisms in their host bacteria. However, it is unclear what factors lead to specific defenses being deployed upon phage infection. To explore this question, we exposed the bacterial fish pathogenFlavobacterium columnareto its virulent phage V156 in the presence of a eukaryotic host signal (mucin). All tested conditions led to some level of innate immunity, but the presence of mucin led to a dramatic increase in CRISPR spacer acquisition, especially in low nutrient conditions where over 60% of colonies had obtained at least one new spacer. Additionally, we show that the presence of a competitor bacterium…
Mast cells as initiators of immunity and host defense
2001
Until recently, mast cells have been viewed primarily as harmful because of their key role as effector cells of allergic and potentially lethal anaphylactic reactions. Their contribution to human health appeared instead to be limited to the elimination of parasites. There is, however, growing evidence for additional beneficial functions of mast cells, particularly regarding the initiation of acquired immune reactions. Thus, mast cells can phagocytize diverse particles, take up antigens, and express a number of receptors, particularly MHC class I and II antigens, ICAM-1 and -3, CD43, CD80, CD86 and CD40L which allow them to interact with T and B lymphocytes. They can also secrete numerous cy…
The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
2017
Abstract:We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain -…
2'-O-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recogn…
2019
Bacterial RNA has emerged as an important activator of innate immune responses by stimulating Toll-like receptors TLR7 and TLR8 in humans. Guanosine 2′-O-methylation at position 18 (Gm18) in bacterial tRNA was shown to antagonize tRNA-induced TLR7/8 activation, suggesting a potential role of Gm18 as an immune escape mechanism. This modification also occurs in eukaryotic tRNA, yet a physiological immune function remained to be tested. We therefore set out to investigate the immune modulatory role of Gm18 in both prokaryotic and eukaryotic microorganisms, Escherichia coli and Saccharomyces cerevisiae, and in human cells. Using RiboMethSeq analysis we show that mutation of trmH in E. coli, trm…
Physicochemical properties, sugar profile, and non-starch polysaccharides characterization of old wheat malt landraces
2021
Abstract Craft beers produced by small breweries are becoming increasingly popular worldwide due to their unique composition, taste, and flavour. Wheat malt is a traditional brewing raw material with great potential to improve beer properties such as mouthfeel, foam, haze, and flavour. In this study, the malting quality of eight wheat varieties (four common and four durum) was evaluated to explore the feasibility of producing 100 % wheat malt beer from old landraces. The physicochemical characteristics such as friability, Kolbach index, viscosity, and colour, of the wheat malts indicated a better degree of modification in the common wheat varieties when compared to that of the durum wheat v…
Remittance behaviours of foreigners in Italy
2015
This article investigates the determinants of remittance behaviours among foreigners in Italy and intends to gain a better understanding of the temporal pattern of remittances. The analysis is based on data from the 2009 “Italian Statistics on Income and Living Conditions of Households with Foreigners”. The decisions on whether to remit and how much to remit are separately yet simultaneously estimated using a zero-inflated beta regression model. The findings reveal that remittances are driven by a mix of altruistic and self-interest motives that may persist for many years. Many covariates included in the model have a different effect on the propensity to remit and on the relative amount of …
Gamma interferon blocks gammaherpesvirus reactivation from latency in a cell type-specific manner
2007
Gammaherpesviruses are important pathogens whose lifelong survival in the host depends critically on their capacity to establish and reactivate from latency, processes regulated by both viral genes and the host immune response. Previous work has demonstrated that gamma interferon (IFN-gamma) is a key regulator of chronic infection with murine gammaherpesvirus 68 (gammaHV68), a virus that establishes latent infection in B lymphocytes, macrophages, and dendritic cells. In mice deficient in IFN-gamma or the IFN-gamma receptor, gammaHV68 gene expression is altered during chronic infection, and peritoneal cells explanted from these mice reactivate more efficiently ex vivo than cells derived from…