Search results for "IMMUNOLOGY"
showing 10 items of 9651 documents
ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation
2016
ABSTRACT Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro . In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments,…
Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a rando…
2019
PMC6682346; Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naive hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion fol…
Regulating T-cell differentiation through the polyamine spermidine
2021
Background The cross-talk between the host and its microbiota plays a key role in the promotion of health. The production of metabolites such as polyamines by intestinal-resident bacteria is part of this symbiosis shaping host immunity. The polyamines putrescine, spermine, and spermidine are abundant within the gastrointestinal tract and might substantially contribute to gut immunity. Objective We aimed to characterize the polyamine spermidine as a modulator of T-cell differentiation and function. Methods Naive T cells were isolated from wild-type mice or cord blood from healthy donors and submitted to polarizing cytokines, with and without spermidine treatment, to evaluate CD4+ T-cell diff…
The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases
2016
Dysregulation of the intestinal epithelial barrier in genetically susceptible individuals may lead to both intestinal and extraintestinal autoimmune disorders. There is emerging literature on the role of microbiota changes in the pathogenesis of systemic rheumatic diseases such as rheumatoid arthritis, spondyloarthropathies, and connective tissue diseases. Although the role of the gastrointestinal tract in the pathogenesis of spondyloartropathies is well defined and many studies underline the importance of gastrointestinal inflammation in modulating local and systemic inflammation, the data are inconclusive regarding the effect of dysbiosis on rheumatoid arthritis and connective tissue dise…
Formyl-peptide receptor 2 governs leukocyte influx in local Staphylococcus aureus infections
2017
Leukocytes express formyl-peptide receptors (FPRs), which sense microbe-associated molecular pattern (MAMP) molecules, leading to leukocyte chemotaxis and activation. We recently demonstrated that phenol-soluble modulin (PSM) peptides from highly pathogenic Staphylococcus aureus are efficient ligands for the human FPR2. How PSM detection by FPR2 impacts on the course of S. aureus infections has remained unknown. We characterized the specificity of mouse FPR2 (mFpr2) using a receptor-transfected cell line, homeobox b8 (Hoxb8), and primary neutrophils isolated from wild-type (WT) or mFpr2−/− mice. The influx of leukocytes into the peritoneum of WT and mFpr2−/− mice was analyzed. We demonstrat…
Multiple steady states and the form of response functions to antigen in a model for the initiation of T cell activation
2017
The aim of this paper is to study the qualitative behaviour predicted by a mathematical model for the initial stage of T-cell activation. The state variables in the model are the concentrations of phosphorylation states of the T-cell receptor (TCR) complex and the phosphatase SHP-1 in the cell. It is shown that these quantities cannot approach zero and that the model possesses more than one positive steady state for certain values of the parameters. It can also exhibit damped oscillations. It is proved that the chemical concentration which represents the degree of activation of the cell, that of the maximally phosphorylated form of the TCR complex, is, in general, a non-monotone function of…
Protein-protein interactions can be predicted using coiled coil co-evolution patterns
2016
AbstractProtein-protein interactions are sometimes mediated by coiled coil structures. The evolutionary conservation of interacting orthologs in different species, along with the presence or absence of coiled coils in them, may help in the prediction of interacting pairs. Here, we illustrate how the presence of coiled coils in a protein can be exploited as a potential indicator for its interaction with another protein with coiled coils. The prediction capability of our strategy improves when restricting our dataset to highly reliable, known protein-protein interactions. Our study of the co-evolution of coiled coils demonstrates that pairs of interacting proteins can be distinguished from no…
The adaptive value of tandem communication in ants:Insights from an agent-based model
2021
AbstractSocial animals often share information about the location of resources, such as a food source or a new nest-site. One well-studied communication strategy in ants is tandem running, whereby a leader guides a recruit to a resource. Tandem running is considered an example of animal teaching because a leader adjusts her behaviour and invests time to help another ant to learn the location of a resource more efficiently. Tandem running also has costs, such as waiting inside the nest for a leader and a reduced walking speed. Whether and when these costs outweigh the benefits of tandem running is not well understood. We developed an agent-based simulation model to investigate the conditions…
A generalization of Kingman's model of selection and mutation and the Lenski experiment.
2017
Kingman’s model of selection and mutation studies the limit type value distribution in an asexual population of discrete generations and infinite size undergoing selection and mutation. This paper generalizes the model to analyze the long-term evolution of Escherichia. coli in Lenski experiment. Weak assumptions for fitness functions are proposed and the mutation mechanism is the same as in Kingman’s model. General macroscopic epistasis are designable through fitness functions. Convergence to the unique limit type distribution is obtained.
Nature lessons: the whitefly bacterial endosymbiont is a minimal amino acid factory with unusual energetics
2016
Reductive genome evolution is a universal phenomenon observed in endosymbiotic bacteria in insects. As the genome reduces its size and irreversibly losses coding genes, the functionalities of the cell system, including the energetics processes, are more restricted. Several energetic pathways can also be lost. How do these reduced metabolic networks sustain the energy needs of the system? Among the bacteria with reduced genomes Candidatus Portiera aleyrodidarum, obligate endosymbiont of whiteflies, represents an extreme case since lacks several key mechanisms for ATP generation. Thus, to analyze the cell energetics in this system, a genome-scale metabolic model of this endosymbiont was const…