Immune Responses to Persistent or Recurrent Antigens: Implications for Immunological Memory and Immunotherapy

SC was supported by the University of Hull. AP was supported by Miguel Servet CP19/00008 contract from Instituto de Salud Carlos III co-funded by ERDF/ESF, A way to make Europe/Investing in your future.Ye

Dynamic behaviour of Multilamellar Vesicles under Poiseuille flow

Surfactant solutions exhibit multilamellar surfactant vesicles (MLVs) under flow conditions and in concentration ranges which are found in a large number of industrial applications. MLVs are typically formed from a lamellar phase and play an important role in determining the rheological properties of surfactant solutions. Despite the wide literature on the collective dynamics of flowing MLVs, investigations on the flow behavior of single MLVs are scarce. In this work, we investigate a concentrated aqueous solution of linear alkylbenzene sulfonic acid (HLAS), characterized by MLVs dispersed in an isotropic micellar phase. Rheological tests show that the HLAS solution is a shear-thinning fluid with a power law index dependent on the shear rate. Pressure-driven shear flow of the HLAS solution in glass capillaries is investigated by high-speed video microscopy and image analysis. The so obtained velocity profiles provide evidence of a power-law fluid behaviour of the HLAS solution and images show a flow-focusing effect of the lamellar phase in the central core of the capillary. The flow behavior of individual MLVs shows analogies with that of unilamellar vesicles and emulsion droplets. Deformed MLVs exhibit typical shapes of unilamellar vesicles, such as parachute and bullet-like. Furthermore, MLV velocity follows the classical Hetsroni theory for droplets provided that the power law shear dependent viscosity of the HLAS solution is taken into account. The results of this work are relevant for the processing of surfactant-based systems in which the final properties depend on flow-induced morphology, such as cosmetic formulations and food products.Comment: 11 pages, 7 figures. Accepted for publication in Soft Matte

Release of redox enzymes and micro-RNAs in extracellular vesicles, during infection and inflammation

Many studies reported that redox enzymes, particularly thioredoxin and peroxiredoxin, can be released by cells and act as soluble mediators in immunity. Recently, it became clear that peroxiredoxins can be secreted via the exosome-release route, yet it remains unclear how this exactly happens and why. This review will first introduce briefly the possible redox states of protein cysteines and the role of redox enzymes in their regulation. We will then discuss the studies on the extracellular forms of some of these enzymes, their association with exosomes/extracellular vesicles and with exosome micro-RNAs (miRNAs)/mRNAs involved in oxidative processes, relevant in infection and inflammation

IL-7 unveils pathogen-specific T cells by enhancing antigen-recall responses

BACKGROUND: IL-7 promotes the generation, expansion and survival of memory T cells. Previous mouse and human studies showed that IL-7 can support immune cell reconstitution in lymphopenic conditions, expand tumor-reactive T cells for adoptive immunotherapy and enhance effector cytokine expression by autoreactive T cells. Whether pathogen-reactive T cells also benefit from IL-7 exposure remains unknown. METHODS: Here we investigated this issue in cultures of peripheral blood mononuclear cells (PBMCs) derived from patients infected with various endemic pathogens. After short-term exposure to IL-7, we measured PBMC responses to antigens (Ag) derived from pathogens, such as Mycobacterium tuberculosis (MTB), Candida albicans (Ca) and Cytomegalovirus (CMV), and to the superantigen Staphylococcus aureus enterotoxin B (SEB). RESULTS: We found that IL-7 favoured the expansion and, in some instances, the uncovering of pathogen-reactive CD4 T cells, by promoting pathogen-specific IFNɣ, IL-2 and TNF recall responses. CONCLUSIONS: Our findings indicate that IL-7 unveils and supports re-activation of pathogen-specific T cells with possible diagnostic, prognostic and therapeutic significance, of clinical value especially in conditions of pathogen persistence and chronic infectio

Diffusion induced anisotropic cancer invasion: A novel experimental method based on tumor spheroids

Tumour invasion is strongly influenced by microenvironment and, among other parameters, chemical stimuli play an important role. An innovative methodology for the quantitative investigation of chemotaxis in vitro by live imaging of morphology of cell spheroids, in 3D collagen gel, is presented here. The assay was performed by using a chemotactic chamber to impose a controlled gradients of nutrients (glucose) on spheroids, mimicking the chemotactic stimuli naturally occurring in the proximity of blood vessels. Different tumoral cell lines (PANC-1 and HT-1080) are compared to non-tumoral ones (NIH/3T3). Morphology response is observed by means a Time-lapse workstation equipped with an incubating system and quantified by image analysis techniques. Description of invasion phenomena was based on an engineering approach, based on transport phenomena concepts. As expected, NIH/3T3 spheroids are characterized by a limited tendency of cells to invade the surrounding tissue, unlike PANC-1 and HT-1080 that show relatively stronger response to gradients.Comment: 14 pages, 9 figure

Beyond the Umbrella. A Systematic Review of the Interventions for Prevention of and Reduction in the Incidence and Severity of Ovarian Hyperstimulation Syndrome in Patients Who Undergo In Vitro Fertilization Treatments

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for the prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analyses of randomized controlled trials (RCTs) and assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identified, analyzed in terms of safety/efficacy ratio and risk of bias, and graded using the Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In the IVF population not at a high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of a GnRH antagonist may reduce OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have been shown to be promising

i-Rheo-optical assay: Measuring the viscoelastic properties of multicellular spheroids

This study introduces a novel mechanobiology assay, named “i-Rheo-optical assay”, that integrates rheology with optical microscopy for analysing the viscoelastic properties of multicellular spheroids. These spheroids serve as three-dimensional models resembling tissue structures. The innovative technique enables real-time observation and quantification of morphological responses to applied stress using a cost-effective microscope coverslip for constant compression force application. By bridging a knowledge gap in biophysical research, which has predominantly focused on the elastic properties while only minimally exploring the viscoelastic nature in multicellular systems, the i-Rheo-optical assay emerges as an effective tool. It facilitates the measurement of broadband viscoelastic compressional moduli in spheroids, here derived from cancer (PANC-1) and non-tumoral (NIH/3T3) cell lines during compression tests. This approach plays a crucial role in elucidating the mechanical properties of spheroids and holds potential for identifying biomarkers to discriminate between healthy tissues and their pathological counterparts. Offering comprehensive insights into the biomechanical behaviour of biological systems, i-Rheo-optical assay marks a significant advancement in tissue engineering, cancer research, and therapeutic development

Compressional stress stiffening & softening of soft hydrogels - how to avoid artefacts in their rheological characterisation

Hydrogels have been successfully employed as analogues of the extracellular matrix to study biological processes such as cells' migration, growth, adhesion and differentiation. These are governed by many factors, including the mechanical properties of hydrogels; yet, a one-to-one correlation between the viscoelastic properties of gels and cell fate is still missing from literature. In this work we provide experimental evidence supporting a possible explanation for the persistence of this knowledge gap. In particular, we have employed common tissues' surrogates such as polyacrylamide and agarose gels to elucidate a potential pitfall occurring when performing rheological characterisations of soft-materials. The issue is related to (i) the normal force applied to the samples \textit{prior} to performing the rheological measurements, which may easily drive the outcomes of the investigation outside the materials' linear viscoelastic regime, especially when tests are performed with (ii) geometrical tools having unbefitting dimensions (i.e., too small). We corroborate that biomimetic hydrogels can show either compressional stress softening or stiffening, and we provide a simple solution to quench these undesired phenomena, which would likely lead to potentially misleading conclusions if they were not mitigated by a good practice in performing rheological measurements, as elucidated in this work

Impact of surfactant polydispersity on the phase and flow behavior in water: the case of Sodium Lauryl Ether Sulfate

This study delves into the impact of molecular polydispersity on the phase behavior of Sodium Lauryl Ether Sulfate (SLES) surfactant, aiming to deepen understanding of its implications for fundamental science and industrial applications. SLE3S is utilized as a model compound: a comprehensive characterization of molecular polydispersity is conducted using Gas Chromatography–Mass Spectrometry and Nuclear Magnetic Resonance spectroscopy, juxtaposing the findings with those for SLE1S. Our comprehensive investigative approach entails: (i) employing Time-Lapse dissolution experiments in microchannel geometries to observe the dissolution and phase transitions; (ii) utilizing polarized light microscopy, confocal microscopy, and Small Angle X-ray Scattering for microstructure identification assessments; (iii) conducting rheological evaluations at various concentrations and temperatures to determine their effects on the surfactant properties. The findings reveal that SLE3S, being more polydisperse, demonstrates complex phase behavior not observed in the less polydisperse SLE1S. Notably, SLE3S exhibits a unique concentration domain, corresponding to a concentration of about 60 %wt, where hexagonal (H), cubic, and lamellar (Lα) phases coexist, resulting in highly viscoelastic heterogeneous mixtures. This behavior is attributed to the local segregation of surfactant components with varying polarity, underscoring the crucial role of molecular polydispersity in the phase behavior of SLES surfactants