Strongyloides stercoralis Infestation in a Child: How a Nematode Can Affect Gut Microbiota

Background: Strongyloidiasis is a neglected tropical disease caused by the intestinal nematode Strongyloides stercoralis and characterized by gastrointestinal and pulmonary involvement. We report a pediatric case of strongyloidiasis to underline the response of the host microbiota to the perturbation induced by the nematode. Methods: We performed a 16S rRNA-metagenomic analysis of the gut microbiota of a 7-year-old female during and after S. stercolaris infection, investigating three time-point of stool samples’ ecology: T₀- during parasite infection, T₁- a month after parasite infection, and T₂- two months after parasite infection. Targeted-metagenomics were used to investigate ecology and to predict the functional pathways of the gut microbiota. Results: an increase in the alpha-diversity indices in T₀-T₁ samples was observed compared to T₂ and healthy controls (CTRLs). Beta-diversity analysis showed a shift in the relative abundance of specific gut bacterial species from T₀ to T₂ samples. Moreover, the functional prediction of the targeted-metagenomics profiles suggested an enrichment of microbial glycan and carbohydrate metabolisms in the T₀ sample compared with CTRLs. Conclusions: The herein report reinforces the literature suggestion of a putative direct or immune-mediated ability of S. stercolaris to promote the increase in bacterial diversity.     

Vaginal Lactobacilli and Vaginal Dysbiosis-Associated Bacteria Differently Affect Cervical Epithelial and Immune Homeostasis and Anti-Viral Defenses

Persistent infection with High Risk-Human Papilloma Viruses (HR-HPVs) is a primary cause of cervical cancer worldwide. Vaginal-dysbiosis-associated bacteria were correlated with the persistence of HR-HPVs infection and with increased cancer risk. We obtained strains of the most represented bacterial species in vaginal microbiota and evaluated their effects on the survival of cervical epithelial cells and immune homeostasis. The contribution of each species to supporting the antiviral response was also studied. Epithelial cell viability was affected by culture supernatants of most vaginal-dysbiosis bacteria, whereas Lactobacillus gasseri or Lactobacillus jensenii resulted in the best stimulus to induce interferon-γ (IFN-γ) production by human mononuclear cells from peripheral blood (PBMCs). Although vaginal-dysbiosis-associated bacteria induced the IFN-γ production, they were also optimal stimuli to interleukin-17 (IL-17) production. A positive correlation between IL-17 and IFN-γ secretion was observed in cultures of PBMCs with all vaginal-dysbiosis-associated bacteria suggesting that the adaptive immune response induced by these strains is not dominated by T_H1 differentiation with reduced availability of IFN-γ, cytokine most effective in supporting virus clearance. Based on these results, we suggest that a vaginal microbiota dominated by lactobacilli, especially by L. gasseri or L. jensenii, may be able to assist immune cells with clearing HPV infection, bypasses the viral escape and restores immune homeostasis.     

Beneficial Effects of Natural Mineral Waters on Intestinal Inflammation and the Mucosa-Associated Microbiota

Natural mineral water (NMWs) intake has been traditionally used in the treatment of various gastrointestinal diseases. We investigated the effect of two French NMWs, one a calcium and magnesium sulphate, sodium chloride, carbonic, and ferruginous water (NMW1), the other a mainly bicarbonate water (NMW2) on the prevention of intestinal inflammation. Intestinal epithelial cells stimulated with heat inactivated Escherichia coli or H₂O₂ were treated with NMWs to evaluate the anti-inflammatory effects. Moderate colitis was induced by 1% dextran sulfate sodium (DSS) in Balbc/J mice drinking NMW1, NWW2, or control water. General signs and histological features of colitis, fecal lipocalin-2 and pro-inflammatory KC cytokine levels, global mucosa-associated microbiota, were analyzed. We demonstrated that both NMW1 and NMW2 exhibited anti-inflammatory effects using intestinal cells. In induced-colitis mice, NMW1 was effective in dampening intestinal inflammation, with significant reductions in disease activity scores, fecal lipocalin-2 levels, pro-inflammatory KC cytokine release, and intestinal epithelial lesion sizes. Moreover, NMW1 was sufficient to prevent alterations in the mucosa-associated microbiota. These observations, through mechanisms involving modulation of the mucosa-associated microbiota, emphasize the need of investigation of the potential clinical efficiency of such NMWs to contribute, in human beings, to a state of low inflammation in inflammatory bowel disease.     

Dietary fish oil n-3 fatty acids increase regulatory cytokine production and exert anti-inflammatory effects in two murine models of inflammation

The higher incidence of inflammatory diseases in Western countries might be related, in part, to a high consumption of saturated fatty acids and n−6 polyunsaturated fatty acids (PUFA) and an insufficient intake of n−3 fatty acids. The purpose of this study was to examine the effects of dietary n−3 fatty acids on innate and specific immune response and their anti-inflammatory action in models of contact and atopic dermatitis. Balb/C mice were fed for 3 wk either n−6 or n−3 PUFA-fortified diets. After inducing a contact or an atopic dermatitis, immunological parameters were analyzed to evaluate the anti-inflammatory potential of these n−3 PUFA. n−3 PUFA reduced innate and specific immune responses through inhibition of T_H1 and T_H2 responses, increase of immunomodulatory cytokines such as IL-10, and regulation of gene expression. The inhibition of both kinds of responses was confirmed by the anti-inflammatory effect observed in contact and atopic dermatitis. Reduction in weight, edema, thickness, leukocyte infiltration, and enhancement of antioxidant defenses in the inflamed ears of mice from both models along with the prevention of delayed-type hypersensitivity induced in atopic dermatitis proved n−3 PUFA efficacy. Our data suggest that dietary fish oil-derived n−3 fatty acids have immunomodulatory effects and could be useful in inflammatory disorders.     

Lipoproteins Are Responsible for the Pro-Inflammatory Property of Staphylococcus aureus Extracellular Vesicles

Staphylococcal aureus (S. aureus), a Gram-positive bacteria, is known to cause various infections. Extracellular vesicles (EVs) are a heterogeneous array of membranous structures secreted by cells from all three domains of life, i.e., eukaryotes, bacteria, and archaea. Bacterial EVs are implied to be involved in both bacteria–bacteria and bacteria–host interactions during infections. It is still unclear how S. aureus EVs interact with host cells and induce inflammatory responses. In this study, EVs were isolated from S. aureus and mutant strains deficient in either prelipoprotein lipidation (Δlgt) or major surface proteins (ΔsrtAB). Their immunostimulatory capacities were assessed both in vitro and in vivo. We found that S. aureus EVs induced pro-inflammatory responses both in vitro and in vivo. However, this activity was dependent on lipidated lipoproteins (Lpp), since EVs isolated from the Δlgt showed no stimulation. On the other hand, EVs isolated from the ΔsrtAB mutant showed full immune stimulation, indicating the cell wall anchoring of surface proteins did not play a role in immune stimulation. The immune stimulation of S. aureus EVs was mediated mainly by monocytes/macrophages and was TLR2 dependent. In this study, we demonstrated that not only free Lpp but also EV-imbedded Lpp had high pro-inflammatory activity.     

The Emerging Role of Non-Coding RNAs in the Regulation of Virus Replication and Resultant Cellular Pathologies

Non-coding RNAs, particularly lncRNAs and miRNAs, have recently been shown to regulate different steps in viral infections and induction of immune responses against viruses. Expressions of several host and viral lncRNAs have been found to be altered during viral infection. These lncRNAs can exert antiviral function via inhibition of viral infection or stimulation of antiviral immune response. Some other lncRNAs can promote viral replication or suppress antiviral responses. The current review summarizes the interaction between ncRNAs and herpes simplex virus, cytomegalovirus, and Epstein–Barr infections. The data presented in this review helps identify viral-related regulators and proposes novel strategies for the prevention and treatment of viral infection.     

Promoting the electromagnetic interference shielding of Ti3C2Tx flakes by loading Fe3O4 nanoparticles: Insights into the performance of oligo-layers exposed to microwave interferences

This study aims to provide insights into the absorption and shielding performances of Fe₃O₄ modified oligo-layered Ti₃C₂T_x towards microwave electromagnetic interference. Oligo-layered Ti₃C₂T_x was modified by Fe₃O₄ nanoparticles (60 nm) via a facile electrostatic assembly approach at different loading rates. This composite was shown to have high dielectric constant and high permeability compared with oligo-layered Ti₃C₂T_x. The microwave electromagnetic absorbing and shielding performances were monitored through a vector network instrument with focuses on the EMI performance. The sample Ti₃C₂T_x/Fe₃O₄ with a 5:1 mass ratio of Ti₃C₂T_x to Fe₃O₄ displayed the optimized EMI shielding performance. The average SE value was 62.19 dB, and the maximum value was 68.72 dB at 18 GHz with a 2.6 mm thickness. The EMI shielding mechanism was understood based on the conductive loss, magnetic loss, dipole polarization, and multiple scattering. Results suggests that Ti₃C₂T_x/Fe₃O₄ composites are expected to be superior EMI shielding material.     

Emerging Evidence for Pleiotropism of Eosinophils

Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.     

Type I Interferon-Mediated Regulation of Antiviral Capabilities of Neutrophils

Interferons (IFNs) are induced by viruses and are the main regulators of the host antiviral response. They balance tissue tolerance and immune resistance against viral challenges. Like all cells in the human body, neutrophils possess the receptors for IFNs and contribute to antiviral host defense. To combat viruses, neutrophils utilize various mechanisms, such as viral sensing, neutrophil extracellular trap formation, and antigen presentation. These mechanisms have also been linked to tissue damage during viral infection and inflammation. In this review, we presented evidence that a complex cross-regulatory talk between IFNs and neutrophils initiates appropriate antiviral immune responses and regulates them to minimize tissue damage. We also explored recent exciting research elucidating the interactions between IFNs, neutrophils, and severe acute respiratory syndrome-coronavirus-2, as an example of neutrophil and IFN cross-regulatory talk. Dissecting the IFN-neutrophil paradigm is needed for well-balanced antiviral therapeutics and development of novel treatments against many major epidemic or pandemic viral infections, including the ongoing pandemic of the coronavirus disease that emerged in 2019.     

Influence of the electrohydrodynamic process on the properties of dried button mushroom slices: A differential scanning calorimetry (DSC) study

In this paper, drying of button mushroom (Agaricus bisporus) slices with an innovative drying technique of hot air combined with Electrohydrodynamic (EHD) drying process was investigated at three electrode gaps (5, 6, and 7 cm) and voltage levels (17, 19, and 21 kV). The effects of different hot air combined with EHD drying treatments on the temperature of the mushroom slices, drying time, final color and protein denaturation features including enthalpy (ΔH), onset temperature (T_o), peak transition temperature (T_p), conclusion temperature (T_c), and temperature range (T_c–T_o) of endothermic peaks were systematically evaluated. In addition, water state changes in DSC cooling thermograms of dried mushroom slices were investigated. The results obtained by differential scanning calorimetry showed that the ΔH values in the DSC traces of the EHD-dried mushroom slices were reduced with a decrease in the electrode gap and an increase in the voltage. Specifically, among voltages of 21, 17, and 19 kV, a voltage of 21 kV resulted in the lowest ΔH and T_c–T_o values and the highest T_p and T_o values. This result indicated that voltage had a significant effect on these responses. Similarly, the DSC results showed a considerable effect of high electric field intensity on ΔH, T_c–T_o and T_p responses related to protein denaturation in comparison to low electric field intensity.     

Poly(?-caprolactone) acrylates synthesized using a facile method for fabricating networks to achieve controllable physicochemical properties and tunable cell responses

We present a facile method to synthesize photo-crosslinkable poly(ε-caprolactone) acrylates (PCLAs) and reveal tunable cell responses to photo-crosslinked PCLAs. Including three PCL diacrylates (PCLDAs) and two triacrylates (PCLTAs), PCLAs could be fabricated into polymer networks with controllable physical properties to satisfy diverse tissue-engineering needs, for example, bone and nerve regeneration. This novel synthetic method used potassium carbonate (K₂CO₃) as the proton scavenger other than widely used triethylamine (TEA) in order to avoid colorization and potential toxicity from the side reaction between TEA and acryloyl chloride. In addition, this new method significantly simplified the purification step of the polymer products because of the convenient separation between inorganic particles and organic polymer solution. Through combining crystallite-based physical network and crosslink-based chemical network together, we could modulate material properties and consequently control cell responses. Thermal properties such as glass transition temperature (T_g), melting temperature (T_m), and crystallinity (χ_c) of both uncrosslinked and crosslinked PCLAs were correlated with their mechanical and rheological properties. Surface characteristics such as surface morphology, hydrophilicity, and its capability of adsorbing serum proteins from cell culture medium were also examined for crosslinked PCLA disks. Mouse MC3T3 cells and rat Schwann precursor cell line (SPL201) cells were applied to evaluate the in vitro biocompatibility of these polymeric networks and the roles of surface chemistry, crystallinity, and stiffness in regulating cell attachment, spreading and proliferation collectively. Semi-crystalline PCLA network with the highest χ_c and T_m was found to support cell attachment, spreading, and proliferation best among all these five systems.     

A Shifted Composition of the Lung Microbiota Conditions the Antifungal Response of Immunodeficient Mice

The microbiome, i.e., the communities of microbes that inhabit the surfaces exposed to the external environment, participates in the regulation of host physiology, including the immune response against pathogens. At the same time, the immune response shapes the microbiome to regulate its composition and function. How the crosstalk between the immune system and the microbiome regulates the response to fungal infection has remained relatively unexplored. We have previously shown that strict anaerobes protect from infection with the opportunistic fungus Aspergillus fumigatus by counteracting the expansion of pathogenic Proteobacteria. By resorting to immunodeficient mouse strains, we found that the lung microbiota could compensate for the lack of B and T lymphocytes in Rag1^–/– mice by skewing the composition towards an increased abundance of protective anaerobes such as Clostridia and Bacteroidota. Conversely, NSG mice, with major defects in both the innate and adaptive immune response, showed an increased susceptibility to infection associated with a low abundance of strict anaerobes and the expansion of Proteobacteria. Further exploration in a murine model of chronic granulomatous disease, a primary form of immunodeficiency characterized by defective phagocyte NADPH oxidase, confirms the association of lung unbalance between anaerobes and Proteobacteria and the susceptibility to aspergillosis. Consistent changes in the lung levels of short-chain fatty acids between the different strains support the conclusion that the immune system and the microbiota are functionally intertwined during Aspergillus infection and determine the outcome of the infection.     

Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status

Little information exists about the evaluation of potential developmental immunotoxicity induced by perfluorooctane sulfonate (PFOS), a synthetic persistent and increasingly ubiquitous environmental contaminant. To assess potential sex-specific impacts of PFOS on immunological health in the offspring, using male and female C57BL/6 mice, pups were evaluated for developmental immunotoxic effects after maternal oral exposure to PFOS (0.1, 1.0 and 5.0 mg PFOS/kg/day) during Gestational Days 1–17. Spontaneous T_H1/T_H2-type cytokines, serum levels of testosterone and estradiol were evaluated in F1 pups at four and eight weeks of age. The study showed that male pups were more sensitive to the effects of PFOS than female pups. At eight weeks of age, an imbalance in T_H1/T_H2-type cytokines with excess T_H2 cytokines (IL-4) was found only in male pups. As for hormone levels, PFOS treatment in utero significantly decreased serum testosterone levels and increased estradiol levels only in male pups, and a significant interaction between sex and PFOS was observed for serum testosterone at both four weeks of age (p_interaction = 0.0049) and eight weeks of age (p_interaction = 0.0227) and for estradiol alternation at four weeks of age (p_interaction = 0.0351). In conclusion, testosterone-mediated endocrine function may be partially involved in the T_H1/T_H2 imbalance induced by PFOS, and these deficits are detectable among both young and adult mice and may affect males more than females.     

Liver-Resident Memory CD8+ T Cells: Possible Roles in Chronic HBV Infection

Achieving a functional cure for chronic hepatitis B virus (HBV) infection or complete elimination of HBV covalently closed circular DNA (cccDNA) has been challenging in the treatment of patients with chronic HBV infection. Although novel antivirals are being investigated, improving HBV-specific adaptive immune responses is also important for durable viral clearance. Tissue-resident memory CD8⁺ T (T_RM) cells were recently reported as a T-cell population that resides in peripheral tissues and does not recirculate. T_RM cells have been studied in the livers of mice and humans. Liver T_RM cells have distinct characteristics compared to T cells in peripheral blood or other tissues, which may be associated with the unique microenvironment of the liver. In this review, we describe the characteristics of liver T_RM cells and their implications in chronic HBV infection. We emphasize that liver T_RM cells can be an immunotherapeutic target for the treatment of chronic HBV infection.     

Perinatal Gram-Positive Bacteria Exposure Elicits Distinct Cytokine Responses In Vitro

During pregnancy, infections caused by the gram-positive bacteria Enterococcus faecalis (E. faecalis), Streptococcus agalacticae (S. agalacticae), and Staphylococcus aureus (S. aureus) are major reasons for preterm labor, neonatal prematurity, meningitis, or sepsis. Here, we propose cytokine responses to bacterial infections by the immature perinatal immune system as central players in the pathogenesis of preterm birth and neonatal sepsis. We aimed to close the gap in knowledge about such cytokine responses by stimulating freshly isolated umbilical blood mononuclear cells (UBMC) with lysates of E. faecalis, S. agalacticae, and S. aureus collected from pregnant women in preterm labor. Bacterial lysates and, principally, S. aureus and S. agalacticae distinctly triggered most of the eleven inflammatory, anti-inflammatory, TH₁/TH₂ cytokines, and chemokines quantified in UBMC culture media. Chemokines depicted the most robust induction. Among them, MIP-1β was further enhanced in UBMC from female compered to male newborn infants. Due to its stability and high levels, we investigated the diagnostic value of IL-8. IL-8 was critically upregulated in cord blood of preterm neonates suffering from infections compared to gestational age-matched controls. Our results provide novel clues about perinatal immunity, underscoring a potential value of IL-8 for the timely detection of infections and suggesting that MIP-1β constitutes an early determinant of sex-specific immunity, which may contribute, e.g., to male’s vulnerability to preterm birth.     

Isothermal crystallization study on aqueous solution of poly(vinyl methyl ether) by DSC method

A study on the isothermal crystallization of water in aqueous solutions of poly(vinyl methyl ether) (PVME) was carried out by the differential scanning calorimetry (DSC). The influence of PVME concentration (49.5, 44.5 and 39.5 v%) and the crystallization temperature (T_c) on crystallization rate G, crystallization enthalpy (ΔH_c) and melting enthalpy (ΔH_m) was investigated. Avrami equation cannot be used to describe the crystallization process of water in aqueous PVME solution. Within the measured temperature range, the crystallization rate G increases with the crystallization temperature T_c and with the decreasing PVME content. The crystallization enthalpy ΔH_c linearly increases with the degree of supercooling. The influence of T_c on the ΔH_c becomes more marked with increasing PVME concentration. For 49.5 and 44.5 v% PVME solutions, the amount of water arrested in solution during the isothermal crystallization and the final concentration of PVME-rich phase increase linearly with the T_c, whereas for 39.5 v% PVME solution, these two values almost do not change with T_c. The amount of frozen water in the subsequent cold crystallization is approximately proportional to the initial T_c. The approximately constant ΔH_m for a given concentration at the different initial isothermal crystallization temperatures suggests that the total amount of ice from the first isothermal crystallization and the second cold crystallization is same. The quantitative relation of the amount of frozen water in the cold crystallization and the initial T_c demonstrates that PVME/water complexes are thermodynamically unstable.     

Biodegradable comb-dendritic tri-block copolymers consisting of poly(ethylene glycol) and poly(l-lactide): Synthesis, characterizations, and regulation of surface morphology and cell responses

A series of well-defined dumbbell-shaped tri-block copolymers consisting of comb-like poly(l-lactide) (PLLA) and linear poly(ethylene glycol) (PEG) with narrow molecular weight distributions and varied PLLA arm lengths have been synthesized via the sequential preparation of terminal dendronized polyhydric PEG and ring-opening polymerization (ROP) of l-lactide (LA). The terminal dendronized polyhydric PEG was prepared by the conjugation of amine-terminated fourth-generation polyester dendrons with NHS-activated PEG followed by the deprotection of acetonide groups. The length of PLLA arms can be readily controlled by the feed molar ratio of LA monomer to the hydroxyl groups in PEG macro-initiator. Differential scanning calorimetric (DSC) measurements and thermal gravimetric analysis (TGA) have been performed to indicate that the glass transition temperature (T_g), melting point (T_m), degree of crystallinity (χ_c), and onset decomposition temperature (T_d) of the copolymers are lower than those of the linear polylactide (LPLLA). Self-organized porous structures have been found in the copolymer films after solution casting and solvent evaporation. Honeycomb-like surface morphology could be achieved by adjusting the length of PLLA arms. Meanwhile, surface chemistry of the copolymer films such as surface hydrophobicity and the capability of adsorbing protein increase with the length of PLLA arms. Controllable material properties have been correlated with the in vitro cell responses. No cytotoxicity of the dumbbell-shaped copolymers has been found using rabbit bone marrow stromal cells (BMSCs). Human embryonic kidney (HEK) 293T cells have been used to reveal the effect of surface characteristics on cell attachment and proliferation. It has been found that cell proliferation has been enhanced significantly on the surfaces of the copolymers with longer PLLA arm lengths because of more favorable surface physicochemical properties.     

Sensitivity of proton NMR relaxation times in a HTPB based polyurethane elastomer to thermo-oxidative aging

Solid-state ¹H NMR relaxometry studies were conducted on a hydroxy-terminated polybutadiene (HTPB) based polyurethane elastomer thermo-oxidatively aged at 80 °C. The ¹H T₁, T₂, and T_1ρ relaxation times of samples thermally aged for various periods of time were determined as a function of NMR measurement temperature. The response of each measurement was calculated from a best-fit linear function of the relaxation time vs. aging time. It was found that the T_2,H and T_1ρ,H relaxation times exhibited the largest response to thermal degradation, whereas T_1,H showed minimal change. All of the NMR relaxation measurements on solid samples showed significantly less sensitivity to thermal aging than the T_2,H relaxation times of solvent-swollen samples.