Search Results (324)

Hantaviruses are emerging zoonotic pathogens responsible for two severe clinical syndromes: (i) haemorrhagic fever with renal syndrome (HFRS) and (ii) hantavirus cardiopulmonary syndrome (HCPS), collectively causing more than 200,000 human cases annually worldwide. Despite their public-health importance, the molecular mechanisms governing the host response and the population-level dynamics of rodent-to-human spillover remain incompletely characterised. The timeliness of this framework is underscored by the April–May 2026 outbreak of Andes orthohantavirus aboard the MV Hondius cruise ship, the first such cluster in a maritime setting, with three deaths reported across multiple countries. This event revealed critical gaps in existing models that treat humans solely as dead-end spillover hosts. Our coupled Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model assumes no human-to-human transmission and is therefore designed for hantavirus strains where spillover does not lead to secondary human cases, specifically Hantaan virus (HTNV), Puumala virus (PUUV), Sin Nombre virus (SNV), and Dobrava-Belgrade virus (DOBV). The Andes virus (ANDV) outbreak aboard the MV Hondius is used as a real-world case study to assess the boundaries of our model and to motivate future extensions, not as a direct validation target for its quantitative predictions. Here, we present an integrated computational study combining three complementary analyses. First, we performed a preliminary phylogenetic analysis of the viral sequence, identifying Orthohantavirus andesense as the likely etiological agent responsible for the vessel-associated outbreak. Second, we carried out a downstream transcriptomic analysis of Hantaan virus (HTNV)-infected human umbilical vein endothelial cells (HUVECs), using publicly available RNA-seq data (GEO accession GSE133751, $n=3$ per group). This analysis identified 184 upregulated and 19 downregulated genes, highlighting a transcriptional response dominated by interferon-stimulated genes (ISGs), including CXCL10, CXCL11, MX2, DDX58, IRF7, STAT1, OASL, and CMPK2. We then constructed a protein–protein interaction (PPI) network using STRING, comprising 176 nodes and 3210 edges, and applied a composite network centrality score to rank putative regulatory hubs. This analysis identified ISG15, IRF1, CXCL10, STAT1, and DDX58 as the most central nodes. Pathway enrichment analysis confirmed a strong activation of interferon signalling (Reactome, $p=1.3\times {10}^{-63}$), antiviral defence mechanisms (Gene Ontology, $p=3.8\times {10}^{-58}$), and NF-$\kappa$B-related pathways, together with a concurrent suppression of ribosomal translation. Finally, we developed a coupled SEIRD epidemiological model that explicitly represents rodent-to-rodent and rodent-to-human transmission with logistic rodent population growth. Preliminary simulation analysis demonstrates that reducing human exposure to rodent excreta is substantially more effective than rodent population control alone for reducing human disease burden, and that rodent control in isolation can paradoxically increase human cases through a dilution-like effect. The integrated framework provides molecular and epidemiological insights relevant to hantavirus surveillance, therapeutic target identification, and public-health intervention design. Full article

Mycobacterium tuberculosis (Mtb) continues to pose a significant global health risk, primarily due to its capacity to modulate host immune responses and achieve prolonged persistence. Recent evidence has increasingly underscored the significance of epigenetic reprogramming as a principal mechanism through which Mtb modifies host cellular functions without altering the fundamental DNA sequence. This review gives a full picture of how Mtb secretory proteins work as nucleomodulins to directly target host chromatin and control gene expression. Mtb uses special secretion systems, such as the ESX (Type VII) and SecA2 pathways, to enable effector proteins to enter host cells. Some of these proteins move to the nucleus and interact with machinery that is linked to chromatin. These nucleomodulins facilitate various epigenetic modifications, encompassing non-canonical histone methylation, DNA methylation, and the modulation of histone acetylation, resulting in extensive transcriptional reprogramming of immune-related genes. These changes make important host defence mechanisms less effective, such as macrophage activation, antigen presentation, cytokine production, and antimicrobial responses. This helps bacteria survive and avoid the immune system. Epigenetic remodeling also affects the polarization and metabolic states of macrophages, which further affect the progression of disease. The reversible characteristics of epigenetic modifications offer a significant prospect for host-targeted therapeutic strategies. Targeting enzymes such as histone deacetylases and DNA methyltransferases has shown potential in restoring immune function and enhancing bacterial clearance, particularly when used in combination with conventional anti-tubercular therapies. Even with these improvements, there are still big problems with fully understanding the functional diversity of Mtb secretory proteins and turning these discoveries into useful medical tools. In general, understanding how Mtb-secreted nucleomodulins and host epigenetic regulation interact is important for understanding how tuberculosis works and finding new ways to treat it. Full article

Chloroplasts are the primary sites of photosynthesis, but growing evidence highlights their broader role as central hubs that coordinate plant responses to environmental challenges. They retain a semi-autonomous genetic system and communicate extensively with the nucleus through anterograde and retrograde signalling pathways, enabling coordinated cellular regulation. Beyond energy conversion, chloroplasts host key biosynthetic pathways and dynamically adjust their metabolic and redox states in response to developmental and environmental cues. This review summarizes the current knowledge of chloroplast functions in response to abiotic and biotic stresses, emphasizing their contribution to plant resilience, productivity and sustainability. Under abiotic stress, chloroplasts undergo structural, metabolic and redox reprogramming to maintain photosynthetic efficiency and metabolic homeostasis. During biotic stress, they act as a powerful signalling platform that integrates immune responses with metabolic and redox regulation. These functions rely on overlapping signalling pathways that are differentially tuned to support acclimation or defence. By coordinating stress responses with photosynthetic activity and metabolic efficiency, chloroplasts play a central role in sustaining plant productivity and represent promising targets for enhancing crop resilience and agricultural sustainability under climate change and increasing pathogen pressure. Full article

Infections in animal production industries can be reduced through targeted breeding of animals with genetically enhanced disease resistance. This type of breeding should be based on a thorough understanding of host defence and its underlying mechanisms. The genes controlling the components of the innate immune system represent a primary target. Their function is highly sensitive to any mutational changes in their structure, which has been optimised through long-term evolution. A source of variability is provided by the polymorphism in the genes encoding components of the Toll signalling pathway as one of the main subsystems of innate immunity. The associated set of genes comprises the group of TLR genes encoding the so-called Toll-like receptors (TLRs), as well as genes encoding other key components of the Toll signalling pathway. Specific attention is paid to the genes encoding the crucial interactors of Toll-like receptors, namely the adaptor MyD88 and other adaptors containing the TIR region. Due to the extremely high evolutionary conservation of this region, any structural variation is expected to have functional consequences on the organismal level. The study of the TLR adaptor MyD88, as well as other related adaptors, has been underestimated in farm animal species, as evidenced by the limited number of research outputs. However, this contrasts with the numerous published functional associations for these genes in human medicine. Such a disparity suggests that further research in this direction in farm animal species may yield novel and important findings in the future. Full article

Skin is a multifunctional organ essential for maintaining body homeostasis, regulating functions and providing protection from environmental stressors. In fish, skin is immune active, containing antimicrobial proteins acting as the first line of defence against infectious pathogens. The gills function similarly, as a key mucosal immunity site, where pathogens induce both innate and adaptive immune responses. In this study, proteomic analysis identified differentially expressed proteins in the skin and gills of ectoparasite Gyrodactylus turnbulli infected guppies (Poecilia reticulata) at two timepoints post-infection (Days 13 and 17). These fish were provided with a health-promoting additive, aimed to boost immunocompetency and reduce ectoparasite infections. Different proteomes were evidenced based on infection status of fish (susceptible, responding, or resistant) and in-feed supplementation. In skin tissue, susceptible fish showed no evidence of immune response, reflecting their high parasite load. Responding fish employed biological processes like apoptosis, reducing the gyrodactylid niche. In resistant fish, up-regulated innate and adaptive immunity explained the low parasite load on the host over the entire infection trajectory. Overall, fish protein expression in the skin and gills was affected both by the dietary supplement and gyrodactylid infection burden, highlighting the role of natural immunostimulants in aquatic infectious disease prophylaxis, control and treatment. Full article

Plant defences are assumed to evolve in response to the negative effects of virus infection on plant fitness (virulence), and to drive plant–virus coevolution. However, viruses are not always antagonistic symbionts of plants, and the expression of defence traits is environment-dependent. Thus, understanding plant–virus interactions requires analysing the expression of defence traits in the host’s native habitat. Here we analyse the effect of cucumber mosaic virus (CMV) infection, and the expression of resistance and tolerance in the native habitat of a wild Arabidopsis thaliana population. Plants from ten genotypes from that population, which have been shown to differ in resistance and tolerance to CMV in a greenhouse, were inoculated with an Arabidopsis isolate of CMV and transplanted to their habitat. Resistance was rated based on virus accumulation in leaves, and tolerance was rated based on the effect of infection on plant fecundity relative to virus accumulation. Consistent with the greenhouse assays, virulence depended on the host genotype, and polymorphisms for resistance and tolerance were expressed in the field, supporting the validity of the conclusions from the greenhouse assays. Our results also support theoretical predictions on the relationships between pathogen multiplication and virulence and between resistance and tolerance. Full article

Powdery scab, caused by Spongospora subterranea, is a major disease of potato in which host resistance remains poorly understood at the biochemical level. While previous transcriptomic and proteomic studies have implicated glutathione S-transferases (GSTs) in cultivar-specific defence responses, orthogonal evidence at the metabolite level remains limited. In this study, untargeted metabolomics was applied to investigate root metabolic responses of two potato cultivars with contrasting resistance to S. subterranea. The relatively resistant cultivar ‘Gladiator’ and the susceptible cultivar ‘Iwa’ were inoculated with S. subterranea, and roots were collected at the stage of visible gall formation for analysis by high-resolution liquid chromatography–mass spectrometry (LC-MS/MS). Principal component analysis revealed a distinct metabolic profile in infected ‘Gladiator’ roots compared with both non-inoculated controls and infected ‘Iwa’ roots, indicating a stronger host metabolic response in the resistant cultivar. Among the annotated metabolites, cysteinyl-glycine (Cys-Gly), a central intermediate of glutathione turnover, was significantly more abundant in infected ‘Gladiator’ roots. The accumulation of Cys-Gly provides direct biochemical evidence linking enhanced glutathione cycling and GST activity to effective host defence. These findings highlight glutathione metabolism as a key component of potato resistance and demonstrate the value of metabolomics for additional validation of biochemical mechanisms underlying plant cultivar responses to biotic stress. Full article

Acinetobacter baumannii is a leading cause of healthcare-associated infections and is classified among the highest-priority antimicrobial-resistant pathogens. Its clinical success reflects the convergence of antimicrobial resistance (AMR) and biological traits that promote environmental persistence and transmission. Acinetobacter baumannii has undergone a remarkable transformation over the past few decades, evolving from a relatively obscure environmental bacterium into a globally recognized multidrug-resistant pathogen. Its prevalence in healthcare settings, particularly intensive care units, has made it a leading cause of ventilator-associated pneumonia, bloodstream infections, wound infections, and urinary tract infections. Beyond its antibiotic resistance, the bacterium’s ability to persist in hospital environments and adapt to host defences has amplified its clinical significance. Recent research has uncovered complex networks of virulence factors, regulatory systems, and metabolic strategies that enable A. baumannii to thrive in hostile environments and evade host immunity, providing new insights into its pathogenesis and potential therapeutic vulnerabilities. This review summarizes the main mechanisms underlying its pathogenicity, including desiccation tolerance, biofilm formation, disinfectant resistance, metal acquisition, motility, and the ability to enter viable but non-culturable states. In A. baumannii, AMR functions as a pathogenesis-adjacent trait, enhancing survival and clonal dissemination through genomic plasticity, resistance islands, efflux systems, and envelope remodeling. Key resistance pathways involve carbapenem-hydrolyzing oxacillinases, metallo-β-lactamases, permeability defects, and multidrug efflux, often coexisting within high-risk clones. From a clinical perspective, management of carbapenem-resistant strains requires accurate infection diagnosis, reliable susceptibility testing, site-specific and PK/PD-optimized therapy, and early reassessment. Overall, the success of A. baumannii reflects the integration of resistance and persistence within healthcare ecosystems, highlighting the need for coordinated strategies combining stewardship, infection control, improved diagnostics, and anti-biofilm or anti-virulence approaches. Full article

The objective of this study was to evaluate the preharvest application of γ-aminobutyric acid (GABA), melatonin (MT), and oxalic acid (OA), at different concentrations and application frequencies, on the physicochemical and microbiological quality of dried figs (cv. Calabacita) at commercial harvest and after 3 and 6 months of refrigerated storage. A further aim was to determine their impact on fungal populations and mycotoxin production. The results showed that untreated dried figs had a higher frequency of Aspergillus welwitschiae, A. tubingensis, and Aspergillus section Flavi, whereas elicitor-treated figs exhibited a lower incidence of toxigenic fungi. A. welwitschiae was the main ochratoxin A (OTA)-associated species detected, although the proportion of OTA-positive figs was lower in elicitor-treated samples than in the control. Aflatoxins (AFs) were detected only sporadically in 2 mM OA treatments, consistent with the limited activity of A. flavus at low storage temperatures. Conversely, Penicillium spp. were widespread but were associated with citrinin (CIT) production only under 2 mM OA treatments. Among the Alternaria toxins, alternariol (AOH) was detected solely in dried figs treated with 1 mM OA. Notably, all investigated mycotoxins were below the limit of detection (<LOD) in dried figs treated with 0.5 mM MT. Moderate elicitor concentrations (e.g., 0.5 mM MT and 50 mM GABA) and multiple preharvest applications generally provided the best balance between fungal suppression and fruit quality, significantly reducing Aspergillus spp. occurrence without promoting the growth of undesirable species. Overall, elicitor treatments decreased the incidence of toxigenic fungi, most likely through direct antifungal effects in senescent dried fruit rather than by inducing host defences. The combined use of preharvest elicitors with appropriate drying and storage conditions is a promising strategy to control fungal contamination and mycotoxin accumulation in dried figs while maintaining quality from preharvest storage. Further research is needed to optimise elicitor concentrations and application timing. Full article

A Group A Streptococcus (GAS, Streptococcus pyogenes) is an exclusively human pathogen whose virulence is driven by a diverse array of surface structures, secreted toxins, and immune evasion mechanisms. Central to its pathogenicity is the M protein, a surface-anchored molecule that inhibits phagocytosis by interfering with complement deposition and binding host factors such as fibrinogen. GAS also secretes a wide range of toxins and enzymes that damage tissues and disrupt host defences. Streptolysin O and streptolysin S are potent cytolysins that lyse immune cells and contribute to tissue necrosis. Pyrogenic exotoxins (such as SpeA and SpeC) act as superantigens, triggering massive, dysregulated T cell activation and cytokine release, an underlying mechanism in streptococcal toxic shock syndrome. Additional factors like DNases and streptokinase facilitate bacterial spread by breaking down host tissue and counteracting neutrophil extracellular traps (NETs). Immune evasion is further supported by the production of enzymes that interfere with complement functions, like the cleavage of chemokines and the targeting of antibodies. Together, these virulence determinants allow GAS to cause a wide spectrum of diseases, ranging from uncomplicated pharyngitis and impetigo to invasive conditions like necrotising fasciitis and sepsis. This review provides a timely overview of the important GAS virulence factors and an update on the current vaccine landscape. Full article

Background/Objectives: Early childhood caries (ECC) and saliva have been studied across disparate domains, including microbiome, fluoride, immune, oxidative-stress, and neuroendocrine research. However, the ECC–saliva literature has not previously been mapped as a connected system using modern natural language processing (NLP). This study treats PubMed titles and abstracts as data to identify major themes, emerging topics, and candidate neuroimmune axes in ECC–saliva research. Methods: Using the NCBI E-utilities API, we retrieved 298 PubMed records (2000–2025) matching (“early childhood caries” [Title/Abstract]) AND saliva [Title/Abstract]. Text was cleaned with spaCy and embedded using a transformer encoder; BERTopic combined UMAP dimensionality reduction and HDBSCAN clustering to derive thematic topics. We summarised topics with class-based TF–IDF, constructed keyword co-occurrence networks, defined an internal topic-level Novelty Index (semantic distance plus temporal dispersion), and mapped high-novelty topics to gene ontology and Reactome pathways using g:Profiler. Prophet was used to model temporal trends and forecast topic-level publication trajectories. Finally, we generated a fully synthetic neuroimmune salivary dataset, based on realistic ranges from the literature, to illustrate how the identified axes could be operationalised in future ECC cohorts. Results: Seven coherent ECC–saliva topics were identified, including classical microbiome and fluoride domains as well as antioxidant/redox, proteomic, peptide immunity, and Candida–biofilm themes. High-novelty topics clustered around total antioxidant capacity, glutathione peroxidase, superoxide dismutase, and peptide-based host defence. Keyword networks and ontology enrichment highlighted “Detoxification of Reactive Oxygen Species”, “cellular oxidant detoxification”, and cytokine-mediated signalling as central processes. Temporal forecasting suggested plateauing growth for classical epidemiology and fluoride topics, with steeper projected increases for antioxidant and peptide-immunity themes. A co-mention heatmap revealed a literature-level Candida–cytokine–neuroendocrine triad (e.g., Candida albicans, IL-6/TNF, cortisol), which we propose as a testable neuro-immunometabolic hypothesis rather than a confirmed mechanism. Conclusions: AI-assisted topic modelling and network analysis provide a reproducible, bibliometric map of ECC–saliva research that highlights underexplored antioxidant/redox and neuroimmune salivary axes. The synthetic neuroimmune dataset and modelling pipeline are illustrative only, but together with the literature map, they offer a structured agenda for future ECC cohorts and mechanistic studies. Full article

Factor XII is a molecule of unclear physiological function that has attracted increasing research interest across multiple medical disciplines. In recent years, a substantial body of evidence has emerged regarding the contribution of factor XII to the pathogenesis of inflammatory and prothrombotic conditions. FXII has been shown to play a protective role in FXII-driven coagulation during host defence against infections and to protect against multi-organ failure in animal models of sepsis. In acute respiratory distress syndrome (ARDS), FXII activity contributes to the release of pro-inflammatory mediators and is associated with severe clinical outcomes; it also induces fibroblast migration in idiopathic pulmonary fibrosis. FXII deficiency has been associated with reduced neutrophil adhesion and migration in sterile skin wounds and immune complex-induced vasculitis. In neurological conditions, FXII deficiency significantly reduced the number and severity of multiple sclerosis relapses and decreased the volume of post-traumatic brain oedema. In heart failure pathogenesis, FXII deficiency and pharmacological inhibition of FXII activity blocked activation of the renin–angiotensin–aldosterone system (RAAS) in dilated cardiomyopathy, increased median survival, and delayed heart failure onset in murine models. Importantly, FXII inhibition prevented arterial thrombosis without affecting haemostasis. This review summarises the latest findings on the contribution of FXII to inflammatory and prothrombotic states across multiple medical fields, including cardiology. Pharmacological inhibition of FXII has generated considerable interest as a potential future therapeutic strategy; however, to date, human studies remain limited. Full article

Chlamydia trachomatis has a significant impact on public health, especially among adolescents and young women; it primarily affects urogenital epithelial cells, leading to cervicitis and urethritis, with >90% of cases showing no symptoms. Consequently, chlamydial infections are commonly misdiagnosed, and, if untreated, they may result in severe reproductive sequelae including infertility. A better understanding of C. trachomatis cell biology and bacterial–host cell interactions may be helpful to identify strategies able to counter its transmission among the population, as well as its dissemination in reproductive tissues, reducing the risk of developing severe reproductive sequelae. Therefore, the present review aims to summarize the evidence on the interplay between C. trachomatis and the host defence factors within the cervicovaginal environment. The sophisticated strategies employed by this clinically significant pathogen to counteract these mechanisms are also discussed. In the literature, the main defence factors include the microbiota dominated by Lactobacillus crispatus and several molecules like lactoferrin, able to protect the cervicovaginal microenvironment against C. trachomatis through several mechanisms (e.g., EB coaggregation and competitive exclusion, as well as anti-inflammatory activity). However, the major player in clearing chlamydial infections remains the interferon-gamma (IFN-γ) produced by natural killer and T cells, via the depletion of critical nutrients for C. trachomatis such as tryptophan, or via the ubiquitylation and destruction of chlamydial inclusions. Full article

The complement system is a key component of innate immunity, responsible for mediating the rapid clearance of pathogens and coordinating adaptive immune responses. Although complement activation is essential for effective infection control and prevention, its excessive or dysregulated function contributes to the pathogenesis of various immune-mediated disorders. Therefore, therapeutic inhibition of the overactive complement cascade, in which specific components are selectively blocked to suppress pathological activation, plays an important role in the treatment of various complement (immune)-mediated diseases. This article provides an overview of complement inhibition as a therapeutic strategy, highlighting the infectious risks associated with its use. Disruption of complement-dependent host defence mechanisms increases the risk of invasive infections (caused by encapsulated pathogens, e.g., Neisseria spp., Streptococcus pneumoniae and Haemophilus influenzae type B), which represent a significant clinical challenge. Therefore, the use of complement inhibition should not only be effective but also safe in combination with the application of all possible tools to prevent infections. Strategies, such as vaccination and antibiotic prophylaxis, are crucial to minimise these complications, despite the persistence of the risk of breakthrough infections. Furthermore, this review examines advancements in patient risk stratification, evaluates alternative preventive measures, and identifies key gaps in current clinical practice. Future directions include improving monitoring protocols, creating more selective or locally acting complement inhibitors, and implementing biomarker-driven personalised therapies that maximise benefits while reducing side effects. Full article

Pulmonary involvement in cystic fibrosis (CF) is characterised by respiratory infections caused by bacteria, viruses, and fungi, as well as by dysregulated inflammatory and immune responses. Although essential for the host’s initial defence against these microorganisms, the innate immune response is altered in its main cellular (airway epithelial cells (AECs), monocytes, macrophages, and neutrophils) and molecular (cytokines, chemokines, signal transduction pathways, and transcription factors) components. MicroRNAs (miRNAs) form a regulatory network at the level of inflammatory and immune responses, and their dysregulation has been observed in immortalised and primary CF AECs as well as in monocytes, macrophages, and neutrophils from CF patients. Although the study of individual miRNAs is helping to dissect the specific altered events in CF lung disease (CFLD), large-scale genomic and transcriptomic studies are more likely to capture its full complexity. The studies we identified suggest that miRNAs are involved in various processes related to CFLD, including impaired pathogen response, compensation for hyperinflammation, altered antigen presentation, and wound healing in AECs and macrophages. However, clinical studies involving large cohorts of patients are needed to obtain meaningful results and identify new therapeutic targets. Equally important will be the study of the miRNome as circulating biomarkers for the purposes of diagnostic and prognostic precision medicine. Full article