Search Results (732)

Compelling research has consistently demonstrated a strong relationship between immunometabolism and infectious disease, including the ways in which viral infections alter the metabolic state of immune cells to promote survival. Human immunodeficiency virus (HIV) has been particularly noted for its ability to reprogram the metabolism of cells that contribute to viral persistence. The purpose of this review is to summarize current knowledge of the metabolic state of CD4 T cells and myeloid cells (monocytes/macrophages), two of the primary cell types targeted by HIV. The studies discussed reveal distinct metabolic profiles in both cell types during initial infection, active replication, and latency. In addition, we examine how these metabolic alterations may contribute to the increased frequency and severity of comorbidities observed in people with HIV (PWH). Understanding the impact of HIV infection and latency on immunometabolism may provide deeper insight into long-term viral persistence and support the identification of novel therapeutic targets to reduce chronic inflammation and inform future cure strategies for PWH. Full article

Vaccinations are a cornerstone of primary prevention in pediatric otolaryngology and play a critical role in reducing the burden of pediatric infectious diseases, particularly acute otitis media (AOM) and HPV-related infections. The introduction and widespread use of pneumococcal conjugate vaccines (PCVs) have been associated with substantial changes in the epidemiology of pediatric AOM, particularly through reductions in vac-cine-serotype disease and complicated forms, while contributing to changes in pathogen distribution with an increased role of non-vaccine serotypes and non-pneumococcal bac-teria, requiring continuous epidemiological surveillance. Prophylactic human papillomavirus (HPV) vaccination in adolescents and young adults effectively prevents oral infection with vaccine-type high-risk HPV, a necessary step in the pathogenesis of HPV-related oropharyngeal carcinoma. Clinical and epidemiological studies demonstrate robust antibody responses and significant reductions in oral HPV prevalence among vaccinated individuals. Although direct evidence of a reduction in oropharyngeal cancer incidence is not yet available, vaccination may consequently reduce the future burden of HPV-related oropharyngeal cancers. Long-term surveillance remains essential to confirm this potential benefit. Barriers to optimal vaccine coverage include unequal access, incomplete vaccination uptake, and limited awareness of HPV-related oral disease. In conclusion, vaccinations provide direct and clinically relevant benefits in pediatric otolaryngology by reducing recurrent AOM, severe complications and surgical interventions. HPV vaccination also reduces vaccine-type oral HPV infection and may consequently contribute to reducing the future burden of HPV-related oropharyngeal cancers. Achieving high vaccination coverage, coupled with continuous epidemiological monitoring, is essential to maximize individual and public health benefits and to inform the development of vaccines with broader serotype coverage. Full article

Sex- and gender-based immune differences have often been interpreted through a male–female biological binary, overlooking how endocrine signaling dynamically shapes immune function. Gender-affirming hormone therapy (GAHT) offers a unique physiological model to disentangle the effects of sex steroids from chromosomal background and examine immune plasticity in contexts relevant to reproductive health. This hormone-informed framework proposes that estradiol and testosterone regulate immune set-points across innate, adaptive, metabolic, and mucosal compartments. Through genomic and non-genomic signaling via androgen and estrogen receptors (AR, ERα/β), these hormones drive distinct immune outcomes: testosterone dampens type I interferon responses in plasmacytoid dendritic cells and reshapes monocyte inflammatory profiles, while estradiol promotes macrophage polarization and enhances T helper1 (Th1) responses. Hormonal effects are closely coupled to cellular metabolism: androgen signaling acts as a “metabolic brake” on Th17 cells by limiting glutaminolysis, a process reinforced by epigenetic remodeling, and is reflected in shifts in the circulating metabolome, positioning metabolomics as a sensitive tool for monitoring hormone-driven immune adaptation. Regardless, hormones also reshape mucosal barriers and reproductive microbiome composition. GAHT alters vaginal and gut microbial communities and their metabolism, influencing mucosal immunity, local inflammation, and reproductive tract homeostasis, with potential implications for fertility preservation, susceptibility to reproductive tract infections, and long-term genital mucosal health. Collectively, this evidence underscores that human immunity is highly responsive to endocrine context. This review synthesizes evidence linking endocrine trajectories, tissue microenvironments, reproductive biology, and social determinants of health, aiming to advance understanding of immune plasticity and contribute to a more inclusive framework of human immune diversity. Full article

SARS-CoV-2 infection leads to extrapulmonary complications in multiple organs, including the brain, both in the short-term and long-term. The neurological manifestation of SARS-CoV-2 infection ranges from benign signs like loss of smell and loss of taste to severe complications like encephalitis, stroke, and exacerbation of Alzheimer’s disease (AD) progression. Pericytes are mural cells of the brain vasculature that help maintain the blood–brain barrier (BBB), regulate cerebral blood flow (CBF), modulate neuroinflammation, and clear toxic materials, including amyloid beta. Pericytes express ACE2, the receptor for SARS-CoV-2, and therefore may be targeted by either direct virus infection or virus-induced inflammatory cytokines induced by the virus in the brain. To further study the effects of SARS-CoV-2 on pericytes and BBB integrity, the long-term effects of SARS-CoV-2 infection on brain pericytes, inflammation, and other neuropathological complications were analyzed in mice. K18 (human ACE2 transgenic) mice were infected with 10³ PFU of SARS-CoV-2 (delta strain), and the brains were analyzed at 6, 14, and 30 days post-infection (dpi). A significant reduction in the weight of infected mice was observed by 6 dpi. Viral nucleocapsid protein and infectious SARS-CoV-2 were observed in the brains of all mice by 6 dpi, and in some mice by 14 dpi, but not at 30 dpi. This observation suggests viral neurotropism with subsequent clearance at later timepoints. Despite virus clearance, the levels of inflammatory mediators, including TNF-α and IFN-γ were significantly elevated up to 30 dpi. We also observed a significant reduction in the level of brain pericytes by 14 dpi up to 30 dpi. Importantly, an increase was observed in the level of Friend Leukemia Integration 1 (FLI-1), a transcription factor known to promote pericyte cell death, from 14 dpi up to 30 dpi. The level of amyloid beta 1–42 was elevated in the brain of infected mice at 6 dpi, and this was maintained up to 30 dpi, and there was a decrease in neuronal density from 14 to 30 dpi. Furthermore, we observed an increased expression of Alzheimer’s disease (AD)-associated genes like PSEN1, BACE1, and APP. Furthermore, there was increased activation of several neurodegenerative pathways, including “G alpha (z) signaling pathway”, “Apelin muscle signaling pathway”, and “G beta-gamma (Gβγ) signaling”, in the brains of infected mice compared to control mice. Collectively, the observed neuropathology and unique molecular markers of neurodegenerative disease progression provide a novel mechanism by which COVID-19 may promote dementia/AD by contributing to pericyte loss and BBB dysfunction during infection. Full article

Graft failure and graft-versus-host disease are the main limiting factors for the engraftment of not only xenogeneic but also allogeneic grafts. Long-term engraftment of human immune cells in mice with severe combined immunodeficiency and IL2rg deletion is key to the success of long-term studies in modeling human immunodeficiency virus (HIV) infection. Human peripheral blood mononuclear cells were injected intravenously into males of one strain and females of two other strains of immunodeficient mice. Before the injection of human cells, mice of each strain were irradiated with three different doses. Interleukin-2 was administered to 50% of mice within 5 days of human cell injection. Its effect was assessed by monitoring graft-versus-host disease, survival, complete blood count (CBC) indices, quantification of human cells in whole blood, pathological changes, and immunohistochemical detection of human cells in tissues. Furthermore, the applicability of correlating immune-inflammation indices with mouse body weight (BW) dynamics, graft-versus-host disease (GVHD) progression, degrees of chimerism and human T-helper cells was determined for the first time. As a result of this work, a panel of biomarkers was developed for predicting the long-term welfare of mice with elements of the human immune system (HIS) in long-term studies, including HIV testing. Full article

The Powassan virus (POWV) is a neurovirulent tick-borne virus that causes age-associated lethality and long-term neurologic sequelae in 50% of survivors. In aged mice the POWV strain LI9 mirrors human lethality and neuropathology; however, an avirulent POWV mutant, LI9-D308N, fails to enter the CNS or cause lethal disease. The D308N mutation is present in an envelope protein domain associated with cell attachment, yet the role of D308N mutations in cell tropism and neuroinvasion remains to be resolved. Here, we engineered fluorescent mScarlet3 and mNeonGreen reporter genes into WT LI9, and avirulent LI9-D308N viruses and assessed their ability to infect CNS cells in vitro. In addition, we generated replication-defective reporter POWVs that only replicate in NS1-expressing cells by replacing NS1 with fluorescent genes. Similar to WT LI9, fluorescent reporter POWVs spread focally and nonlytically, are stable following passage and reach high titers 2–5 dpi. In NS1-expressing VeroE6 cells, LI9-ΔNS1-FL reporters exhibited robust fluorescence 24 h post-infection (hpi), while fluorescence from LI9-reporter infections was first observed ~32 hpi. Comparing LI9-mScarlet3 and avirulent LI9-D308N-mScarlet3 viruses revealed no difference in their ability to infect human brain microvascular endothelial cells, pericytes, astrocytes, microglia or neuronal cells in vitro. Notably, LI9-mScarlet3 viruses productively and persistently infected differentiated, neuron-like, SH-SY5Y cells without apparent cytotoxicity. These findings indicate that LI9-D308N is capable of infecting blood–brain-barrier and CNS cells, and suggest that neuroinvasion is restricted prior to LI9-D308N engaging CNS cells. These results are consistent with clearance of LI9-D308N from the blood, or the D308N mutation interfering with potential routes of POWV neuroinvasion. Collectively, fluorescent POWV reporter viruses provide insight into the mechanism of POWV neuroinvasion, permit analysis of replication-defective POWVs as vaccines and provide a means of analyzing POWV cell tropism, antivirals and cell-to-cell spread in BSL2 and BSL3 settings.: Full article

This study developed an eco-epidemiological model incorporating constant prey refuge, predator disease transmission, and anthropogenic harvesting to explore the coupled dynamical behaviors of ecological populations under natural infection and human interference. All feasible equilibrium points of the proposed system were solved, and the local stability of the boundary equilibria and threshold conditions for transcritical bifurcations were systematically analyzed. The global asymptotic stability of the positive coexistence equilibrium was verified by constructing the appropriate Lyapunov functions. Furthermore, a parameter sensitivity analysis was performed to identify the dominant parameters governing population persistence and system stability. To balance ecological sustainability and economic benefits, an optimal harvesting control problem was investigated, and time-dependent optimal harvesting efforts were obtained by applying optimal control theory. Numerical simulations demonstrated that the optimal harvesting strategy can dynamically adjust the harvesting intensity to maximize long-term discounted economic profit while maintaining stable population coexistence. The theoretical and numerical results provide reliable theoretical guidance for the sustainable exploitation and ecological management of infected predator–prey ecosystems. Full article

Human intestinal nematode infections (HINIs) remain a public health concern despite reduced prevalence following mass drug administration (MDA) in low- and middle-income countries. Children continue to bear a substantial burden of infection, and caregiver knowledge and practices may influence their risk of acquiring infection. Sustaining control during the transition of prevention programmes to surveillance-based strategies requires an understanding of behavioural determinants of transmission. Therefore, we assessed caregiver knowledge, attitudes, and practices (KAP) and their associations with sociodemographic characteristics and child infection status. A community-based cross-sectional study was conducted among 945 caregivers of primary school children in Anuradhapura, a low-prevalence setting where school-based MDA ceased in 2019, to assess caregiver KAP and child HINI status. An interviewer-administered questionnaire assessed KAP, sociodemographic, water, sanitation, hygiene (WASH), and behavioural factors. Participants were predominantly mothers (89.5%). Good knowledge was observed in 61.7%, positive attitudes in 95.6% and good practices in 99.2%. Knowledge gaps persisted regarding transmission and complications. Higher caregiver knowledge (OR = 0.52; 95% CI: 0.36–0.72) and regular deworming (OR = 0.58, 95% CI: 0.40–0.83) were associated with lower odds of infection, whereas attitudes and practices were not independently associated. Caregiver knowledge remains a key determinant of infection risk. Gaps in knowledge, misconceptions, and practices may sustain transmission even in low-prevalence settings. Strengthening health education, school-based hygiene promotion, and community engagement remains essential to reinforce preventive behaviours and support long-term control as countries transition from routine MDA to elimination-oriented strategies. Full article

Healthcare-associated infections are prevalent in hospitals, clinics, and long-term care facilities. The use of wound dressings on active skin wounds, like burns, can cause damage to the skin barrier when removed for cleaning. Electrospun biodegradable and biocompatible membranes have emerged as promising alternatives for wound dressing applications. In the present study, an electrospun membrane composed of polyvinyl alcohol/kefiran/schizophyllan loaded with gentamicin and ascorbic acid was developed. Kefiran was obtained from kefir with a 0.61% extraction yield. Beadless electrospun membranes with a diameter of 400 nm were obtained. Antimicrobial activity of the membrane against Staphylococcus aureus and Pseudomonas aeruginosa was determined. Growth inhibition halos of 16.4 ± 2.2 mm were found for Pseudomonas aeruginosa. Furthermore, the membrane cytocompatibility assay of the membrane showed no cell toxicity in human dermal fibroblasts (HDFn cells). The produced membranes showed potential to be used as a wound dressing material in the future. Full article

Fluoroquinolones are broad-spectrum, bactericidal antibacterial agents used in both human and veterinary medicine. Some human-approved drugs are used off label in veterinary medicine while veterinary-approved drugs are not used in humans. Veterinary-approved fluoroquinolones are used on both food and companion animals and against a wide range of clinical indications including infections of the urinary tract, respiratory tract, skin and skin structure, mammary gland and others. Not all veterinary-approved fluoroquinolones have the same clinical indication and it is important to understand these important differences. A recently approved for food animals agent called pradofloxacin is characterized as being dual targeting in that it simultaneously inhibits DNA gyrase (topoisomerase II) and Topoisomerase IV—two enzymes critical for DNA replication. Simultaneous targeting of two enzymes is argued to reduce the likelihood for resistance selection. This article reviews veterinary-approved fluoroquinolones including an overview of the drugs, in vitro activity including bactericidal properties, pharmacokinetic/pharmacodynamics, antimicrobial resistance, anti-inflammatory properties and clinical trial results. Appropriate use of this important class of antimicrobial agents is essential for clinical success and long-term viability of these compounds. Full article

Objective: This systematic review aimed to evaluate the effects of biomimetic surface engineering strategies applied to dental implants on osseointegration and peri-implant bone regeneration compared with conventional implant surfaces. Materials and Methods: A comprehensive literature search was conducted in the Web of Science, PubMed, and Scopus databases in accordance with the PRISMA guidelines, covering the period from January 2021 to January 2026. A total of 12 studies, including in vivo animal experiments and in vitro investigations, that met the inclusion criteria were analyzed. Risk of bias assessment was performed using the SYR-CLE tool and the ARRIVE guidelines. Results: Biomimetic strategies, including laser texturing, sulfonation, bioactive coatings, and growth factor/peptide functionalization (e.g., BMP-2, FGF-2, and PRF), significantly increased bone–implant contact (BIC), new bone volume (BV/TV), and biomechanical stability (pullout strength and reverse torque) compared to conventional surfaces. These surfaces enhance fixation under conditions of low bone density, such as osteoporosis, and improve infection resistance through antibacterial activity. In addition, these modifications enhance cellular adhesion, osteogenic differentiation, angiogenesis, and immune modulation. Conclusions: Current experimental evidence suggests that biomimetic implant surface engineering transforms dental implants from passive biomaterials into multifunctional bioactive interfaces capable of simultaneously regulating osteogenesis, immune response, angiogenesis, and antibacterial activity. Although promising outcomes have been demonstrated in preclinical studies, standardized long-term human clinical studies are still required to validate translational potential and long-term clinical efficacy. Full article

This review describes a novel method for increasing the effectiveness of inactivated enveloped whole-virus vaccines by targeting them for extensive uptake by antigen-presenting cells (APCs). Several inactivated whole-virus vaccines with dense glycan shields display suboptimal effectiveness because the multiple carbohydrate chains (glycans) on the virus mask immunogenic peptides and surround the virus with a negative electrostatic charge that decreases uptake by APCs. It is postulated that engineering such vaccinating viruses to present the carbohydrate antigen “α-gal epitope” on the glycan shields will immunocomplex them with the anti-Gal antibody; thus, it will target them for robust uptake by APCs. Anti-Gal is an abundant natural antibody in humans, constituting ~1% of human circulating immunoglobulins. The ligand of anti-Gal is the α-gal epitope, which is naturally synthesized in non-primate mammals and New World monkeys by the glycosylation enzyme α1,3galactosyltransferase. This enzyme is encoded by the GGTA1-gene. Viral vaccines presenting multiple α-gal epitopes on their glycan shield bind anti-Gal and activate the complement system to produce complement chemotactic cleavage peptides C5a and C3a that induce extensive recruitment of APCs to vaccine injection sites. The virion-bound anti-Gal further targets the viral vaccine for robust uptake by APCs, following binding of its Fc “tail” to Fcγ-receptors on APCs. The efficacy of this method was studied in anti-Gal-producing mice with α-gal presenting inactivated influenza virus vaccine and with gp120 of HIV presenting this epitope. These studies indicated that virus vaccines engineered to present α-gal epitopes increase anti-virus antibody production and virus-specific T-cell activation by 15- to 100-fold in comparison to the same vaccines lacking α-gal epitopes. It is suggested that α-gal presenting inactivated SARS-CoV-2 virus vaccines can induce a similar protective long-term immune memory against S- M-, E-, and N-viral proteins. Furthermore, immune-escaping variants of the mutated S-protein may be destroyed by antibodies to M and E proteins, and cells infected with such variants may be killed by cytotoxic T cells specific to peptides of the N-protein. Such an anti-M-, E-, and N-protein immune protection may prevent expansion of these variants and thus may avoid the need for immunization with COVID-19 vaccines every 6 months or following the appearance of new variants. A similar potent immunization may be achieved with an inactivated Ebolavirus vaccine engineered to present α-gal epitopes on the glycan shield. The resulting immune response to the various Ebolavirus proteins also may contribute to cross-reactive protection against other Ebolavirus species containing proteins with evolutionarily conserved structures. An effective method for the preparation of a whole-virus vaccine presenting α-gal epitopes is by arming it with the GGTA1-gene inserted into the viral genome. Such virions will present multiple α-gal epitopes on their glycan shield, which will amplify their immunogenicity instead of reducing it in the wild-type virus. Full article

Plague remains a significant natural focal zoonotic infection with continuing epidemiological relevance in the Republic of Kazakhstan. This study provides a comprehensive assessment of epizootological dynamics in natural plague foci during 2020–2025 through the integration of historical epidemiological data, phenotypic and molecular characterization of Yersinia pestis, and GIS-based spatial analysis. The study utilized long-term surveillance data (1920–2025), epidemiological records of human plague cases (1926–2003), phenotypic analysis of 1526 strains, and whole-genome sequencing of 75 representative isolates. Epizootological monitoring demonstrated high surveillance coverage and stable monitoring capacity, together with a marked increase in the application of molecular diagnostic methods. By 2025, both the number and isolation rate of Y. pestis strains increased substantially, while the epizootically active area expanded in 2024–2025, although the overall long-term trend in active area was not statistically significant. Despite these fluctuations, Y. pestis populations remained highly stable, with 94.9% phenotypically typical and 97.5% genotypically typical strains, and no evidence of antimicrobial resistance. Spatial autocorrelation analysis using Moran’s I revealed significant clustering of epizootics (Moran’s I = 0.1627; z = 4.39; p < 0.001), indicating non-random spatial distribution and localized zones of increased epizootic activity. No human plague cases have been recorded since 2003 during the period of sustained epidemiological surveillance and control measures. These findings highlight the potential utility of integrating spatial modeling and molecular surveillance into risk-oriented plague monitoring and control strategies. Full article

Background: Hepatitis B and C viral infections remain a significant global health challenge, despite the implementation of an effective direct-acting antiviral (DAAs) and nucleos(t)ide analogues (NAs). Current HBV therapy is not curative as stopping therapy usually leads to active disease in most patients requiring long-term treatment. Although current HCV-DAAs are highly effective they fall short due to arising drug-resistance and have limited ability to avert re-infections. Furthermore, current HCV DAA treatments lead to the reactivation of occult HBV infection, compromising the effectiveness of current antiviral therapies, and increasing the risk of severe liver complications like cirrhosis and hepatocellular carcinoma. In addition, current treatments do not restore the immune dysfunction, a characteristic of chronic HBV infection. Given the global burden of disease, there is an urgent need for more effective therapy that can shorten the duration of treatment and achieve high rates of HBsAg reduction. Combining an antiviral to reduce viral antigen burden and an immunomodulator to boost the immune response could provide an effective treatment for HBV/HCV infections. Methods: In this study, we explored the potential of a novel bacterial therapeutic agent, heat-killed Caulobacter crescentus (HKCC), as an alternative and/or adjunct host-based therapy for HCV and HBV infections. Here, we have investigated the antiviral effects of the HKCC-stimulated human PBMCs using in vitro HCV and HBV infection models to assess viral replication, viral relapse responses, protein expression, and cytotoxicity. Results: Our findings reveal that HKCC induced a multi-functional cytokine response (IFN, TNF, IL-2, IL-10, IL-6, IL-17A, and IL-22) in PBMCs obtained from multiple healthy donors. Supernatants collected from these HKCC-stimulated human PBMCs, alone and in combination with antivirals, strikingly inhibited HCV replication and viral relapse responses without inducing any cytotoxic effects on HCV-1a replicon cells. In addition, these PBMC supernatants, with or without antivirals, led to the suppression of HBV DNA replication and inhibited HBsAg and HBeAg production in HepG 2.2.15 cells. Conclusions: In conclusion, HKCC is a promising candidate for eliminating HBV and HCV infections, and warrants further investigation to potentially contribute to the development of a novel host-based immunotherapy. Full article

Toxoplasmosis remains one of the most common parasitic infections affecting humans, with significant implications for pregnancy and fetal health. Maternal primary infection during gestation can result in transplacental transmission of Toxoplasma gondii, leading to a wide spectrum of congenital disease. The risk of vertical transmission increases with gestational age, whereas disease severity is inversely related—early infections causing severe neurological and ocular damage, and late infections often resulting in subclinical forms. Advances in serological testing, including IgG avidity assays and molecular diagnostics such as PCR on amniotic fluid, have improved early detection and management. Prenatal treatment with spiramycin or pyrimethamine–sulfadiazine–folinic acid combinations has been associated with reduced transmission and less severe fetal disease in several studies, although the magnitude of benefit remains debated. Long-term follow-up is essential, as late-onset manifestations, particularly chorioretinitis and neurodevelopmental impairment, are common. This narrative review was based on a comprehensive literature search of major medical databases and summarizes current knowledge on the epidemiology, pathophysiology, diagnosis, treatment, and outcomes of toxoplasmosis in pregnancy. Particular emphasis is placed on high-prevalence countries, where greater parasite genetic diversity, distinct epidemiological patterns, and a higher burden of congenital disease pose unique clinical and public health challenges. Despite progress in understanding parasite biology, pathogenesis, and treatment efficacy, congenital toxoplasmosis continues to be underdiagnosed and underreported, especially in low-resource settings. Ongoing challenges include optimizing screening strategies, ensuring access to standardized therapies, and strengthening surveillance systems. Full article