Abstract: Dengue infection remains a major global health concern, with a subset of patients progressing from self-limited dengue fever to severe disease characterized by plasma leakage, shock, and organ dysfunction. The dengue non-structural protein 1 (NS1), a multifunctional glycoprotein expressed on infected cells and secreted into circulation, has emerged as a key mediator linking viral infection to immune-driven vascular pathology. This review synthesizes experimental, animal, and human clinical evidence on NS1-driven immunopathogenesis, focusing on mechanisms leading to endothelial dysfunction and increased vascular permeability. NS1 modulates the complement system in a context-dependent manner, contributing to immune evasion by inhibiting terminal complement complex formation, while also promoting antibody-dependent complement activation associated with severe disease. Additionally, NS1 directly disrupts endothelial barrier integrity through disruption of adherens and tight junction architecture, Ang-2/Tie2 imbalance, activation of RhoA/ROCK signalling, and enzymatic degradation of the endothelial glycocalyx, with further amplification through inflammatory mediators. In addition, evidence is integrated showing that NS1 activates innate immune signaling, perturbs platelet biology and haemostasis, forms pro-inflammatory complexes with lipoproteins. Moreover, anti-NS1 antibodies may be both protective and pathogenic. Collectively, these data position NS1-linked pathways as rational targets for adjunctive therapies and next-generation vaccines aimed at preventing vascular leakage and severe dengue infection.

Abstract:

Angiostrongyliasis, the primary cause of eosinophilic meningitis, represents an emerging disease caused by Angiostrongylus cantonensis larvae, inadvertently transmitted to humans. The diagnosis of human angiostrongyliasis relies on epidemiological features, clinical symptoms, medical history, and laboratory findings, notably hyper eosinophilia in blood and cerebrospinal fluid. Consequently, accurate diagnosis is challenging and prone to confusion with other parasitic diseases. The quest for an early, rapid, and specific diagnostic test for angiostrongyliasis persists, driven by the imperative for enhanced test specificity. Material and Methods: This study focused on the mapping of IgM epitopes within galectin-1 (Gal-1) and galectin-2 (Gal-2) proteins derived from A. cantonensis. The specificity of the epitopes was assessed using database homology analysis. After selecting specific epitopes, researchers chemically synthesized 12 individual MAPs4 peptides and one chimeric polypeptide that is 58 amino acids long. The effectiveness of these synthesized peptides was subsequently evaluated using ELISA. Results: A total of twelve unique IgM epitopes were discovered; four were linked to Gal-1, while eight linked to Gal-2. An ELISA-peptide method confirmed the twelve epitopes, and then the chimeric polypeptide was employed as an antigen to coat ELISA plates. This setup was evaluated with patients' sera to diagnose strongyloidiasis in vitro. Conclusions: This study provides a comprehensive representation of the IgM epitopes of Gal-1 and Gal-2 from A. cantonensis. ELISA data utilizing chimeric the polypeptide demonstrate that the selected sequences hold promise for the development of a specific immunological assay tailored for the acute diagnosis of angiostrongyliasis infections.

Abstract: Background/Objectives: Patients receiving maintenance hemodialysis (HD) commonly exhibit malnutrition, chronic low-grade inflammation, and metabolic disturbances. Gut dysbiosis may contribute to these abnormalities through the gut-kidney axis. This study aimed to characterize gut microbiota composition in HD patients and examine its associations with demographic, clinical, and body composition parameters. Methods: This cross-sectional study included 96 patients with end-stage kidney disease on maintenance HD. Clinical, laboratory, inflammatory, nutritional, and bioimpedance-derived body composition data were collected, including Malnutrition-Inflammation Score (MIS). Stool samples were analyzed for gut microbiota composition. Associations with host-related variables were assessed using alpha- and beta-diversity analyses, subgroup comparisons, and Mantel testing. Results: Gut microbiota showed marked inter-individual heterogeneity at the genus level, with dominant taxa including Blautia, Faecalibacterium, Streptococcus, Gemmiger, Ruminococcus, Escherichia-Shigella, and Enterococcus. Chao1 richness was higher in men than in women. Shannon entropy and Chao1 richness were positively associated with age and visceral adipose tissue (VAT), while Faith’s phylogenetic diversity increased with age. In contrast, the Gini index was negatively associated with age and VAT, indicating a more even microbial structure in older individuals and those with higher visceral adiposity. Beta-diversity differed between men and women and across categories within the female subgroup. Mantel testing showed a modest but significant correlation between microbiota and metadata distances. Conclusions: Gut microbiota in maintenance HD patients is highly heterogeneous and associated mainly with sex, age, visceral adiposity, and overall host phenotype. These findings suggest that microbiota variation in HD reflects multidimensional host-related factors rather than a single clinical feature.

Abstract: Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are among the most significant respiratory diseases, and their significant syndemic interaction in epidemiology during the pandemic period has raised severe global healthcare concerns. Disruption of TB control programs, potential co-infection and common risk factors underscore the need for a systematic assessment of the connection between these diseases. We summarize the current information regarding the relationship between tuberculosis (TB) and COVID-19 during and following the pandemic, including epidemiology; potential pathophysiological connections between SARS-CoV-2 infection and TB; clinical outcomes; and the implications for management. Global estimates of the burden of both diseases are reviewed, along with reported rates of TB–COVID-19 co-infection and associated mortality. The authors discuss mechanistic aspects of Mycobacterium tuberculosis and SARS-CoV-2 immune responses, including how these infections could modulate host immunity, thus impacting susceptibility and outcomes of disease upon co-infection. This review additionally discusses mutually shared risk factors and the broader implications of the COVID-19 pandemic on TB diagnosis, treatment sustainability and public health initiatives. The review also includes current therapeutic approaches and preventive strategies such as vaccination and integrated disease management. Overall, the evidence indicates that the overlap of TB and COVID-19 presents significant diagnostic, clinical and broader public health challenges, especially in settings of high burden. To reduce the combined burden of these infections and restore momentum towards global TB control targets, strengthening surveillance and respiratory disease management, as well as research on immune interactions and long-term outcomes will be the key.

Abstract: Micro- and nanoplastics (MNPs) have now been detected in human blood, placenta, and arterial tissue, yet the oral cavity, which serves as the primary portal of environmental exposure, has received strikingly little mechanistic attention. This narrative review addresses that gap from an environmental microbiology perspective, synthesizing recent literature on periodontal disease, chronic low-grade inflammation, oral biofilms, dental materials, microbial–plastic interactions, and systemic chronic disease risk. Unlike prior reviews, we apply an explicit evidentiary framework that distinguishes what is directly demonstrated from what is biologically plausible but unproven, and we situate the periodontal environment specifically as a particle-retention and inflammatory-amplification niche. The strongest direct oral evidence shows that human dental calculus harbors at least 26 microplastic types, dominated by polyamide (41.4%), polyethylene (32.7%), and polyurethane (7.0%). Polyethylene isolated from calculus induces cytotoxicity, apoptosis, impaired migration, NF-κB activation, and upregulation of IL-1β and IL-6 in human gingival fibroblasts. The oral cavity is also a portal for environmental exposure and a local site of plastic generation: MNPs are released from chewing gum, oral care products, orthodontic appliances, and resin-based dental materials, while oral microorganisms have been documented to degrade methacrylate polymers. Across experimental systems, MNPs activate oxidative stress, inflammasome signaling, macrophage polarization, and barrier dysfunction — pathways that overlap extensively with the pathobiology of periodontitis. Environmental biofilm studies further indicate that plastic substrates can enhance extracellular polymeric substance production, quorum sensing, antibiotic resistance gene transfer, and pathogen persistence, suggesting a plausible but not yet proven oral plastisphere within plaque and calculus. We argue that periodontitis should be reconceptualized as a chronically inflamed particle-processing interface that may increase local MNP retention, cellular reactivity, and systemic inflammatory spillover, with implications for cardiovascular, metabolic, and other chronic disease risk pathways. Current evidence does not yet prove that environmental MNP exposure causes human periodontitis, and that evidentiary boundary is maintained throughout. A priority research agenda is proposed, centered on contamination-controlled subgingival biomonitoring stratified by periodontal status, spatially resolved multi-species biofilm models, polymer source attribution, and longitudinal clinical studies linking oral plastic burden to inflammatory and systemic outcomes.

Abstract:

Polyols are widely used as non-cariogenic sweeteners in foods and oral care products, yet their comparative activity against diverse oral microbes and their potential relevance to the oral–systemic axis remain incompletely defined. Here, we performed an in vitro, optical-density (OD)-based screening of four polyols—allulose, D-mannose, erythritol, and xylitol—against Streptococcus mutans, Streptococcus anginosus, Candida albicans, and Fusobacterium nucleatum. Cultures were grown with polyols at 1–20% (w/v), and OD600 was recorded at organism-specific endpoints (~24 h). Allulose, erythritol, and xylitol produced strong, concentration-dependent suppression of streptococcal growth at ≥5–10%, whereas C. albicans showed minimal changes across the tested range. F. nucleatum was highly sensitive to allulose, D-mannose, and xylitol at ≥5% (reducing OD to ≤13% of untreated control), while low concentrations of D-mannose and erythritol increased OD above control, suggesting species-specific utilization or stress responses. One-way ANOVA with Tukey’s HSD post hoc testing supported significant between-polyol differences for most concentrations in Streptococcus spp. and F. nucleatum. Collectively, these results identify polyol- and taxon-specific growth phenotypes that can inform the formulation of swallow-safe oral hygiene products and motivate follow-up work in polymicrobial biofilm models and clinical studies targeting oral inflammation and downstream systemic risk.

Abstract: Background/Objectives: The aim of the paper is to assess the impact of HPV DNA on the survival and cure rates of patients with newly diagnosed head and neck cancers who underwent surgery and subsequent adjuvant radiotherapy. Methods: The study group consisted of 28 patients (55%) with squamous cell carcinoma of the oral cavity and 23 patients (45%) with squamous cell carcinoma of the oropharynx. All 51 patients underwent primary surgical treatment, extended by adjuvant radiotherapy in 33 patients (65%). Cases with cT2 (n=23; 45%) and cN0 (n=25; 49%) were the most common. Twenty-seven patients (53%) were HPV-positive, including 14 (27%) patients with squamous cell carcinoma of the oral cavity and 13 (25%) with squamous cell carcinoma of the oropharynx. Twenty-one patients (41%) were HPV positive p 16 (+). The Kaplan-Meier method was used to assess 3-year overall survival (OS) and 3-year locoregional control (LRC) in the study group, depending on tumor location and HPV status. Results: The 3-year OS rates in the group of HPV-positive and HPV-negative patients with oral cavity tumors were 80% and 82%, respectively; p=0.965, while in the group of HPV-positive and HPV-negative patients with oropharyngeal cancer, the 3-year OS rates were 100% and 67.5%, respectively; p=0.045. In patients with oropharyngeal cancer, the 3-year LRC rates for HPV-positive and HPV-negative patients were 100% and 59%, respectively; p=0.059. In the group of patients with oral cavity cancer, 3-year LRC rates for HPV-positive and HPV-negative subjects were 55% and 52%, respectively; p=0.771. 3-year OS for HPV-positive p16 (+) and HPV-positive p16 (-) was 88% and 78%, respectively; (p=0.965). In the whole study group, HPV-negative patients were more often offered adjuvant treatment compared to HPV-positive patients. Conclusions: The 3-year OS rates of patients with cancers of the oral cavity and the oropharynx treated with combined therapy in the study group did not differ statistically significantly depending on HPV status. HPV-positive patients with oropharyngeal cancer had better 3-year OS and LRC rates compared to HPV-negative patients. Patients with HPV-dependent oropharyngeal cancer, no statistically significant improvement in 3-year OS was observed compared to patients with HPV p16 (+) vs HPV p 16 (-). However, in the group of patients with oral cavity cancer, HPV status did not show prognostic significance.

Abstract: Molecular mimicry — structural or sequence similarity between pathogen-derived and host self-peptides sufficient to trigger cross-reactive immune responses — has been proposed as a mechanism of autoimmune triggering across rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, antiphospholipid syndrome, dermatomyositis, and Guillain-Barré syndrome. Computational identification of mimicry candidates has historically relied on sequence-based metrics, resting on the untested assumption that sequence similarity predicts structural similarity at the MHC-presented peptide level. We present MimicryDB-Auto, to our knowledge the first curated, labelled multi-pathogen dataset integrating MHC epitope prediction, sequence alignment, and atomic structural validation at the individual epitope level across both MHC class I and II presentations, comprising 399 pathogen-host peptide pairs spanning 32 organisms constructed through a reproducible seven-step pipeline. Following structural validation using TM-align with RMSD < 2.0 Å, 262 pairs were classified as confirmed unbound structural mimics and 137 as non-mimics. Within the confirmed mimic pool, sequence identity explained at most 1.6% of variance in structural RMSD at both the 2.0 Å threshold (r = −0.127, p = 0.036, n = 272) and the stricter 1.0 Å threshold (r = −0.046, p = 0.562, n = 159) — a relationship of no practical predictive utility across threshold definitions. A Random Forest classifier trained exclusively on sequence and immunological features achieved AUC-ROC = 0.958 (95% CI: 0.886–0.999), confirming a multivariate sequence signal exists but is insufficient as a standalone substitute for structural validation. Cross-pairing validation further confirmed that 99.2% of structurally equivalent non-matched pairs had zero detectable sequence similarity, quantifying the scope of sequence-dissimilar structural mimicry invisible to conventional screening. All structural comparisons were performed on unbound peptide conformations, representing a proxy for MHC-presented structure rather than direct immunological validation. MimicryDB-Auto and the complete pipeline are publicly available at https://github.com/minbaku/molecular-mimicry-RA-pipeline.

Abstract: Manganese (Mn²⁺) is an essential trace element within organisms spanning the entire tree of life. It has reported that Mn²⁺ exerts strong immunocompetence and exhibits antiviral effects against various human and animal viruses, including DNA and RNA viruses. Recently, Mn²⁺ has recently been found to be involved in the activation of the innate immune DNA-sensing cGAS-STING pathway and subsequent anti-virus function. However, the antiviral mechanism of Mn²⁺ remains unclear. In current study, the results suggested that cGAS-STING pathway is essential for Mn²⁺ promoting the IFN signaling, but it is not essential for triggering antiviral functions. After knocking out the STING or IRF3 gene, Mn²⁺ still retains its antiviral activity against HSV-1 and VSV. Furthermore, the results from transcriptomic analysis indicated that Mn²⁺ could induce a significantly change of apoptotic process in STING⁻/⁻ 3D4/21 cells. Mn²⁺ could induce cell apoptosis through oxidative stress pathway, and inhibiting the apoptotic signal could suppress the Mn²⁺-mediated antiviral activity in STING⁻/⁻ 3D4/21 cells. Additionally, dual knockout of IRF3 and caspase3 resulting in concurrent loss of IFN and apoptotic signals eliminate the antiviral effects of Mn²⁺. In summary, the current study has suggested that Mn²⁺ could exert antiviral effects not only through the cGAS-STING-IFN pathway but also via the ROS-apoptosis pathway.

Abstract: The relationship between microorganisms and human health is inseparable. In today’s increasingly urbanized world, the relationship between indoor microbial communities and human health is particularly close. Studies have shown that the composition of indoor microbial communities is influenced by various factors, including temperature, humidity, and nutrient conditions. However, research on how to alter indoor microbial community structures by adjusting nutrient components to improve human health is still limited. In this work, we constructed synthetic microbial communities composed of common indoor microorganisms, and analyzed the species composition, metabolic capabilities, antibiotic resistance, and virulence of the microbial communities before and after cultivation using metagenomic sequencing technologies and metatranscriptomic sequencing technologie. Then assessed their community characteristics and evolutionary direction under different nutrient conditions. Overall, when the nutrient conditions in the indoor environment were altered and reduced, the evolutionary direction of indoor microbial communities changed significantly. In-depth research in this field can help improve the composition of indoor microbial communities, thereby benefiting human health and public health construction in urbanized environments.

Abstract: Therapeutic monoclonal antibodies have transformed treatment across cancer, autoimmune disorders, and infectious diseases, yet their clinical utility remains challenged by immunogenicity and the resulting formation of anti-drug antibodies (ADAs), which can alter pharmacokinetics, neutralise therapeutic activity, and cause serious adverse events. This review synthesises current evidence on the mechanisms, prediction frameworks, and mitigation strategies relevant to therapeutic antibody immunogenicity, with particular focus on identifying underexplored risk dimensions not addressed by existing models. We conducted a comprehensive narrative review of peer-reviewed literature covering T-cell-dependent and T-cell-independent ADA formation pathways, multifactorial determinants of immunogenic risk, in silico prediction tools including NetMHCIIpan, SITA, DeepImmuno, and PRIME, in vitro assays including MAPPs and DC-T cell co-culture systems, and engineering and clinical mitigation strategies. Persistent challenges across the field include systematic overprediction, inadequate modelling of conformational B-cell epitopes, HLA diversity, and lack of data standardisation. Critically, molecular mimicry — structural similarity between therapeutic epitopes and pathogen-derived or self-peptides — emerges as a mechanistically distinct and currently invisible risk axis that may explain a subset of inter-patient variability in ADA incidence unaccounted for by existing sequence-based frameworks. Next-generation immunogenicity prediction requires multimodal approaches integrating structural epitope validation, patient HLA profiling, infection history, and machine learning to achieve biologically complete risk stratification.

Abstract: This technical note reports an exploratory, AI-assisted in silico proof of concept implementing a “signaling first, killing later” discovery paradigm: prioritizing compounds with high predicted affinity for bacterial quorum sensing (QS) pathways, then refining them for bactericidal potency. Using Claude Opus 4.6 (Anthropic), a custom SMILES-based descriptor calculator (170+ features) and a four-model ensemble (Random Forest, Gradient Boosting, SVM-RBF, Logistic Regression) were trained on 150 compounds (87 QS modulators, 63 negatives), achieving cross-validated AUC of 0.954 ± 0.024. Screening 218 ZINC15 CEBB tranche compounds identified 101 Tier 1 hits (46.3%), of which 91.1% were nitroaromatic. Bioisosteric modifications rescued 9/15 analogs (60%) as PAINS-clean. An orthogonal antibiotic-likeness model (44 antibiotics vs. 49 non-antibiotics, AUC = 0.809) identified a diacetyl hexahydroxytriphenylene prodrug as dual-high (P_QS = 0.849, P_Abx = 0.876). Six iterative optimization cycles across two phases—structural alert reduction followed by scaffold simplification—produced the final lead M6-12 (SMILES: CNCc1c(F)cc(OC)c2C(OC)C3C(O)CNCC3C(O)c12), a partially saturated fluorinated piperidine-fused tricyclic scaffold. M6-12 achieved: dual-high ML convergence (P_QS = 0.928, P_Abx = 0.792, Joint = 0.735, 4/4 ABX models >0.5), zero PAINS, zero Brenk alerts, zero violations across all five drug-likeness filters, zero CYP inhibition (SwissADME 0/5, pkCSM 0/7), AMES-negative, high GI absorption, and “Very soluble” classification. RDKit validation confirmed: MW = 340.40, Crippen LogP = 0.48, TPSA = 82.98 Ų, HBD = 4, HBA = 6, Fraction Csp3 = 0.647. ChEMBL similarity: 0% at 95% threshold. Property-space MIC estimation: 2–32 μg/mL (Gram-positive), 1–11 μg/mL (Escherichia coli), 33–333 μg/mL (Pseudomonas aeruginosa), with 5/5 Richter rule compliance for Gram-negative penetration. A single pkCSM hepatotoxicity flag—contextualized by zero CYP inhibition, AMES-negative status, and low lipophilicity—probably constitutes the principal limitation requiring in vitro resolution. The signaling-first approach may enrich for molecules operating within biologically relevant chemical spaces, potentially offering a reduction in attrition compared to conventional MIC-first screening. All results require experimental validation.

Abstract: Streptococcus pneumoniae is a leading cause of community-acquired pneumonia, yet the immune mechanisms required for protection against invasive pulmonary infection remain incompletely understood. Using a murine model of homologous protection against invasive pneumococcal pneumonia, we investigated the relative contribution of humoral and cellular immunity through adoptive serum transfer, immune cell depletion, and lung transcriptional profiling. Passive transfer of immune serum conferred robust protection, whereas neutrophil depletion impaired bacterial control, demonstrating that antibodies and neutrophils are key mediators of protection. In contrast, depletion of CD4+ T cells or NK cells did not compromise survival. Although IL-17A has been widely implicated in host defense against pneumococcal infection, IL-17A- deficient mice remained protected, albeit with delayed clearance and reduced early antibody responses. This delay was associated with compensatory upregulation of IL-17F and increased expression of Th1-associated genes in the lung. Together, these findings indicate that IL-17A is not essential for protection and support a model in which coordinated Th1 and Th17-related cytokine responses collectively promote neutrophil recruitment and effective antibody-mediated defense. These results highlight functional redundancy within the IL-17 cytokine axis and suggest that integrated cytokine networks, rather than individual mediators, underpin protective immunity to pneumococcal pneumonia, with implications for next-generation vaccine design.

Abstract: Alphaviruses have recently re-emerged as important disease-causing agents resulting in debilitating disease in humans and animals. To develop therapeutic strategies, it is important to identify host factors co-opted by viruses during infection. Sphingosine kinases (SKs) have been identified as important host factors for viruses. In this study, we extend on our previous findings and demonstrate a pattern to re-localization of sphingosine kinases during alphavirus infection. Specifically, we observed that encephalitic alphaviruses preferentially re-localize SK1, while arthritogenic alphaviruses re-localize SK2, during infection. Inhibition of SK1 specifically resulted in decreased encephalitic alphavirus infection. Thus, sphingosine kinases are differentially recruited by alphaviruses and represent a viable therapeutic target.

Abstract: The occurrence of Escherichia coli resistant to high-priority critically important antimicrobials (HPCIA) in the food chain is a growing concern for food safety and public health. This study aimed to evaluate whether HPCIA-resistant E. coli isolated from pork and chicken meat at retail markets in La Plata, Buenos Aires, Argentina, exhibit source-associated genomic differentiation through whole-genome sequencing. The isolates displayed a polyclonal population structure, encompassing multiple phylogenetic groups and sequence types. Virulence gene profiles were highly diverse, with chicken-derived isolates harbouring a substantially higher number of virulence genes than pork isolates. Notably, one pork isolate carried a complete set of virulence genes characteristic of diarrheagenic E. coli. single Nucleotide Polymorphism-based phylogenetic analysis revealed several closely related subclusters, including strains recovered from both pork and chicken meat from the same retail markets, suggesting recent clonal sharing or cross-contamination at the point of sale. These findings highlight the circulation of genetically diverse HPCIA-resistant E. coli in retail meat, underscoring the potential public health risk and the importance of monitoring resistance and virulence determinants throughout the food production chain.

Abstract: Background/Objectives: Invasive pulmonary mold infections (IPMI) are critical complications in immunocompro-mised patients, contributing significantly to morbidity and mortality. Diagnosing pathogens like Aspergillus and Mucorales remains challenging due to non-specific clinical presentations and the limitations of traditional culture methods. This review provides an up-to-date synopsis of IPMI diagnostic tools, focusing on their diagnostic perfor-mance, turnaround time (TAT), and cost-effectiveness. Methods: We conducted a narrative review of current literature regarding clinical evaluation, radiographic findings (Computerized Tomography), invasive diagnostics (Bronchoalveolar Lavage and biopsy), and non-invasive assays, including next-generation sequencing (NGS) and volatile organic compounds (VOCs). Results: Chest CT remains a vital first step, though classic signs like the "halo" or "reversed halo" are neither sensitive nor specific. Traditional diagnostics are limited by low sensitivity and delayed results. While plasma microbial cell-free DNA (mcfDNA) NGS offers rapid TAT (24–48 hours) and high specificity, its suboptimal sensitivity for Aspergillus (< 50%) and high cost remain significant barriers. Investigational VOC "breath tests" show promising sensitivity (77%–96%) but lack standardization. Conclusions: Future research must prioritize the standardization of non-invasive microbiologic testing modalities, particularly those with rapid TAT such as bedside "breath tests" and high-throughput NGS. Furthermore, the de-velopment of clinical algorithms that balance cost-effectiveness with timely pathogen diagnosis based on the patient’s degree of immunosuppression is essential to improve survival in high-risk populations.

Abstract:

The secondary immunomodulatory effects of conventional therapeutics, such as antibiotics and cytostatics, are frequently overlooked despite their significant clinical implications. Building on our previous findings that drugs like paclitaxel and doxorubicin heavily influence macrophage polarization—potentially driving metastasis or inflammation—this study systematically evaluates the secondary immune-modulating actions of standard drugs and natural adjuvants. Using patient-derived bronchoalveolar lavage (BAL) fluid (ex vivo alveolar macrophages), we developed an analytical platform using synthetic carbohydrate-functionalized fluorescent ligands targeting key receptors (CD206, CD209, CD280, CD301). Integrating ligand-binding profiles with Linear Discriminant Analysis (LDA) yielded quantitative immune-state vectors capable of differentiating between favorable prognostic signatures and imbalanced immune states. Profiling samples across heterogeneous respiratory conditions revealed highly context-dependent responses. While some treatments synergistically corrected imbalanced profiles, others provoked dysregulation. Notably, in pneumonia or bronchitis with an asthma-prone M2-dominant profile, specific antibiotic regimens are critical; doxycycline, for instance, may exacerbate patient deterioration by further driving M2a polarization. Crucially, we identified that natural adjuvants (e.g., curcumin, coumarins, polyphenols) exhibit potent properties capable of correcting these adverse secondary drug effects. Ultimately, this profiling platform highlights the necessity of evaluating patient-specific secondary drug effects, offering a functional blueprint for precision immunotherapy and the rational design of adjuvant-enhanced treatments.

Abstract: Salmonella enterica remains a major threat to animal and human health because of its broad host range, increasing antimicrobial resistance (AMR), and capacity to form biofilms. Biofilm formation enhances bacterial persistence in host tissues, farm environments, food-processing systems, and clinical reservoirs, while also contributing to their tolerance against antibiotics, disinfectants, and other stresses. However, biofilm capacity is not uniform across serovars and is influenced by host adaptation, niche specialization, and accessory genome content. This review synthesizes current knowledge on the relationship between biofilm formation, AMR, and serovar-specific adaptation in Salmonella. It examines biofilm-associated traits across various hosts (e.g., gastrointestinal tract and gallbladder, and environmental (e.g., food-production and clinical) niches, and discusses comparative evidence from genomic, transcriptomic, proteomic, and metabolomic studies. Particular attention is given to the emerging concept of comparative biofilmomics, which integrates phenotypic and multi-omics data across diverse serovars and host sources to identify conserved and niche-specific determinants of persistence. This framework may help define high-risk lineages that couple multidrug resistance (MDR) with enhanced biofilm-forming capacity. A better understanding of these linked traits will support the development of more targeted interventions for controlling persistent Salmonella in veterinary, food production, and public health settings.

Abstract: The incidence of furunculosis in juvenile Atlantic salmon, Salmo salar, has increased in recent years in Chile, with isolates of Aeromonas salmonicida being the primary cause. However, in some cases, molecular diagnostics failed to identify the etiological agent. We previously demonstrated that a proportion of undiagnosed cases was produced by a new A. salmonicida strain. In those cases where the pathogen remained unidentified, we isolated colonies with an A. salmonicida-like appearance. Subsequent phylogenetic analysis presented in this work grouped those A. salmonicida-like isolates within the Aeromonas piscicola clade. Whole genome sequencing confirmed the taxonomic affiliation, giving additional insights into virulence and antibiotic resistance markers. Indeed, one of the strains showed reduced susceptibility to oxytetracycline. Virulence potential was assessed by in vivo testing on S. salar, which resulted in disease with pathognomonic signs of furunculosis. Although the pathogen presents common antigens with A. salmonicida, the current vaccine triggered only a modest IgM response against A. piscicola in the field. Our results support the hypothesis that the incidence of furunculosis in Chile cannot be ascribed to the emergence of the new A. salmonicida strain, but may partially result from infections caused by A. piscicola strains which exhibit a comparable virulence level.

Abstract: Behcet disease (BD) is an inflammatory disorder with manifestation in mucosal tissues. Unlike autoimmune diseases that generate autoantibodies, BD is believed to be an autoinflammatory disease triggered by innate immune cells rather than adaptive cells. Hyperactivation of neutrophils causes vasculitis and thrombosis, and they migrate into cutaneous and ocular lesions. Dominance of M1 macrophages promotes the differentiation of Th1 cells. Moreover, the cross-reaction of bacterial heat shock proteins induces production of cytokines such as IL-4 and IFN-γ, in γδT cells, which alters the balance between Th1 and Th2 phenotypes. Nevertheless, natural killer (NK) cells play more critical roles in BD pathogenesis than other innate immune cells because not only their activity is precisely controlled by the interaction between ligands and receptors but NK1 shift also elicits Th1 dominance. The genetic factors associated with BD are HLA-B51 and major histocompatibility complex class I-related chain A (MICA), which stimulate NK receptors as ligands. Improperly processed peptides dysregulate their interaction with NK receptors, triggering the inflammatory response. NK1 and NK2 subsets represent cytokine production in relapse and remission periods; however, the cytotoxicity of NK cells in relapse is lower than that in remission periods. It still remains unclear how NK cells are activated recurrently and expand cytokine production. This review highlights the regulation of gene expression encoding NK receptors, tissue-resident NK cells, and adaptive NK cells to discuss their potential for relapsing. Splicing variants and readthrough genes encoding NK receptors easily alter cytokine production. Moreover, tissue-resident NK cells in mucosal tissues and adaptive NK cells that memorize the virus infection have the potential to trigger hyperactivation in relapse.