Search Results (9,450)

Lyme disease (LD) is classically defined as a tick-borne infection caused by Borrelia burgdorferi sensu lato (Bbsl). However, accumulating evidence indicates that, beyond microbial persistence, Bbsl infection can initiate sustained immune dysregulation and post-infectious inflammatory phenotypes in a subset of patients. This narrative review integrates open-access experimental, translational, and clinical data and discusses LD within the spectrum of infection-triggered, immune-mediated processes. We review key immunopathogenic mechanisms, including dysregulated innate immune activation, type I interferon (IFN-I) signaling, T helper 1 and T helper 17 (Th1/Th17) polarization with regulatory T-cell (Treg) insufficiency, antigen persistence (notably borrelial peptidoglycan), and pathways linking infection to autoimmunity such as molecular mimicry, epitope spreading, and human leukocyte antigen (HLA)-restricted susceptibility. These mechanisms are integrated with immune-mediated clinical manifestations affecting the central nervous system (CNS), peripheral nervous system (PNS), musculoskeletal system, heart, skin, and hematologic compartment. Finally, we discuss translational implications for diagnosis, biomarker-guided stratification, and emerging therapeutic strategies that extend beyond antimicrobial therapy, while addressing current controversies and limitations. This framework supports a mechanistic model in which Lyme disease-associated morbidity in selected patients reflects persistent immune activation and dysregulated host responses triggered by infection. Full article

Tuberculosis–diabetes mellitus (TB-DM) is increasingly recognized as a syndemic in which chronic metabolic dysregulation amplifies tuberculosis severity, delays treatment response, and increases relapse and mortality. However, conventional systemic correlates soluble cytokines and bulk whole-blood transcriptomic signatures often appear broadly similar between TB and TB-DM. This highlights a key gap: clinically meaningful immune dysfunction in TB-DM likely resides in specific lung and blood cell states that are poorly resolved by bulk assays. Small extracellular vesicles (EVs) in plasma and bronchoalveolar lavage (BAL) provide a tractable “liquid biopsy” layer because their RNA and protein cargo can integrate information from infected macrophages, neutrophils, and epithelial/endothelial compartments, and may also include pathogen-derived components. Yet most EV studies remain bulk and cell-agnostic, and interpretation is constrained by heterogeneous vesicle mixtures, selective cargo packaging, and co-isolated non-vesicular contaminants, issues that are especially problematic for nucleic-acid claims without rigorous controls. In this targeted narrative review (2010–2026), we argue that single-cell and multimodal immune reference atlases, including scRNA-seq/CITE-seq, provide a needed scaffold to link EV cargo patterns to specific immune cell states, pathways, and anatomic compartments in TB-DM, enabling prioritized candidates and testable hypotheses. We outline three complementary frameworks: reference-atlas anchoring to project EV cargo modules onto atlas-defined immune states; orthogonal triangulation combining computational inference with immunoaffinity enrichment, targeted validation, and functional assays; and cautious use of “droplet-era” extracellular signals as hypothesis-generating priors for EV-producing states. Implemented in longitudinal, clinically annotated cohorts with standardized EV workflows, atlas-guided EV profiling could yield cell-of-origin–resolved biomarkers of TB-DM immunopathology and treatment response, while prioritizing mechanistically plausible targets for host-directed intervention. Full article

Larix olgensis, a keystone timber species in Northeast China, is increasingly threatened by Neofusicoccum laricinum-induced shoot blight, a devastating disease that compromises forest health and necessitates sustainable management strategies. Here, we demonstrate that the endophytic bacterium Bacillus amyloliquefaciens JL54 elicits multifaceted defense responses in L. olgensis, enhancing resistance to pathogen infection. Greenhouse assays revealed that JL54 pretreatment reduced disease incidence by 12.5% and achieved 43.75% control efficacy while maintaining host vigor. Histochemical analyses identified JL54-induced rapid hydrogen peroxide (H₂O₂) accumulation, extensive lignin deposition, and localized programmed cell death (PCD), indicative of a primed immune response. Transcriptomic analyses uncovered distinct temporal defense patterns: early-stage responses (0 h post-inoculation) were characterized by upregulation of cutin, suberin, and wax biosynthesis pathways, reinforcing physical barriers, whereas late-stage responses (12 h post-inoculation) were dominated by ribosome- and proteostasis-related pathways (e.g., heat shock proteins [HSPs], glutathione S-transferases [GSTs]) to mitigate cellular damage. Biochemical assays corroborated these findings, with JL54 colonization reducing membrane lipid peroxidation (27.2% decrease in malondialdehyde content) and significantly elevating the activity of key defense enzymes, including peroxidase (POD), phenylalanine ammonia-lyase (PAL), and GST. Phytohormone profiling implicated jasmonic acid (JA) as the central mediator of induced systemic resistance (ISR), with JL54-potentiated JA signaling preceding pathogen containment. Collectively, these results demonstrate that JL54 contributes to a coordinated defense strategy in L. olgensis, integrating structural reinforcement (cuticle/lignin), oxidative stress management, and JA-mediated immune priming. These insights advance the understanding of endophyte-conferred resistance in conifers and highlight JL54’s potential as a biocontrol agent for sustainable forestry. Full article

Pseudomonas plecoglossicida causes bacterial hemorrhagic ascites in ayu (Plecoglossus altivelis), a lethal disease characterized by abdominal distension with hemorrhagic ascites, multifocal organ hemorrhages, and histopathologically evident hepatocellular necrosis and inflammatory infiltration. The lack of effective treatments exacerbates mass mortalities, posing a significant threat to aquaculture. Given the severe pathogenesis of P. plecoglossicida infection—which involves bacterial colonization, tissue necrosis, and host immune dysregulation—effective therapeutic strategies are urgently needed. Through a screen of traditional Chinese medicine monomers, we identified harmine, an indole alkaloid derived from Peganum harmala seeds, as a potent agent against this pathogen. In vivo, harmine exhibited direct bactericidal activity by disrupting membrane integrity, as evidenced by increasing membrane permeability, and inhibiting biofilm formation. In an ayu infection model, harmine significantly increased host survival, reduced tissue bacterial load, and enhanced innate immunity by augmenting monocyte/macrophage phagocytosis and bactericidal capacity while suppressing pro-inflammatory cytokine release and apoptosis. Mechanistically, the Drug Affinity Responsive Target Stability assay was used to identify the molecular target of harmine, followed by functional validation through PRDX6−knockdown experiments. Harmine exhibited direct bactericidal activity by disrupting membrane integrity and inhibiting biofilm formation. In the ayu infection model, harmine significantly increased host survival, reduced tissue bacteria1 load, and enhanced innate immunity by augmenting monocyte/macrophage system and bactericidal capacity while suppressing pro-inflammatory cytokine release and apoptosis, the latter likely through modulation of PRDX6−mediated oxidative stress and downstream caspase signaling. Mechanistically, DARTS revealed that harmine binds to peroxiredoxin 6 (PRDX6), a multifunctional enzyme possessing peroxidase, phospholipase A₂, and lysophosphatidylcholine acyltransferase activities. This binding liberates TNF receptor-associated factor 6 (TRAF6), facilitating its mitochondrial translocation and association with the ECSIT signaling integrator complex, thereby amplifying mitochondrial reactive oxygen species (mROS) production and potentiating macrophage-mediated bacterial killing. These findings establish harmine as a promising therapeutic candidate for controlling P. plecoglossicida infections and underscore the value of host-directed immunomodulation derived from natural products in aquaculture medicine. Full article

Periodontitis is a chronic inflammatory disease driven by microbial dysbiosis and an exacerbated host immune response. This leads to progressive breakdown of periodontal tissues. Although scaling and root planing remains the standard treatment, its capacity to fully restore immune balance and host–microbiota homeostasis is limited. Probiotics have emerged as promising adjunctive strategies to modulate pathways involved in periodontal disease progression. This review aimed to evaluate current clinical evidence on the use of probiotics as adjuncts in periodontal therapy. The review followed the Scale for the Assessment of Narrative Review Articles criteria, applied exclusively as a reporting-quality framework. A literature search was conducted in MEDLINE via PubMed for manuscripts indexed through January/2026, using MeSH terms related to periodontitis and probiotics. Probiotics demonstrate potential as adjunctive agents in periodontal therapy, as evidenced by improvements in clinical parameters (probing depth, clinical attachment level, and/or bleeding on probing) reported in clinical studies. However, the findings remain heterogeneous across trials. Variability in probiotic strains, CFU concentrations, administration routes, and treatment durations highlights the need for standardized clinical protocols to improve comparability and reproducibility and better establish their clinical efficacy. Stronger, long-term evidence is required to standardize therapeutic protocols. Full article

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Beyond genetic and proteostatic mechanisms, infection- and dysbiosis-based models of AD have gained renewed attention, including the antimicrobial protection hypothesis, in which Aβ may participate in innate immune defense. Here, we reanalyzed ribosomal depleted (Ribo-Zero) RNA-seq data from dorsolateral prefrontal cortex (DLPFC) samples from the Mount Sinai Brain Bank cohort (GSE53697) to screen for non-human transcripts. Reads underwent quality control and adapter trimming, taxonomic classification with Kraken2, abundance re-estimation with Bracken, and differential abundance testing with edgeR. Across 17 samples (9 advanced AD and 8 controls), we detected low-biomass microbial signals, with Acinetobacter radioresistens showing enrichment in the AD group (FDR = 0.018). Several additional taxa showed suggestive group differences but did not remain significant after multiple testing correction, including Lactobacillus iners (FDR = 0.051). We also performed an exploratory in silico analysis of an A. radioresistens biofilm-associated protein homolog, identifying predicted amyloidogenic motifs and surface-exposed regions that may be relevant to cross-seeding hypotheses, although no mechanistic inference can be drawn without experimental validation. Given the technical challenges of inferring microbial signals from post-mortem brain RNA-seq data, including contamination risk, low microbial biomass, and overwhelming host background, these findings should be interpreted as hypothesis-generating and warrant orthogonal validation in larger, microbiome-aware cohorts. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for hepatocellular carcinoma (HCC); however, a considerable proportion of patients do not achieve durable clinical benefits. This highlights the need for reliable predictive biomarkers, which are currently lacking. The accumulated evidence supports a relevant role of the gut–liver axis in modulating immunotherapy outcomes, and several studies have identified distinct microbial features associated with either responders or non-responders. Responders to immunotherapy frequently present with higher microbial diversity and enrichment of beneficial taxa, whereas the expansion of pro-inflammatory and pathogenic bacteria has been associated with primary resistance and increased treatment-related toxicity in non-responders. However, the available findings remain heterogeneous across cohorts, likely owing to differences in geography, diet, liver disease etiology, treatment regimens, and microbiome analytical methods. Machine-learning models integrating metagenomic and metabolomic data have shown encouraging results in defining microbial signatures associated with treatment outcomes, although variability among cohorts currently limits their clinical applicability and generalizability. Beyond microbial taxonomic composition, microbiota-derived metabolites—such as short-chain fatty acids, bile acids, inosine, and tryptophan catabolites—appear to play a crucial role in shaping the tumor microenvironment and host immune responses, thus representing additional candidate biomarkers, also due to the relative ease of their measurement. Finally, microbiota-targeted interventions are emerging as potential strategies to enhance immunotherapy efficacy. Overall, the gut microbiome and its metabolic activity represent promising tools, albeit still under investigation, for patient stratification and personalized management in HCC treated with ICIs. Therefore, this review aims to summarize and critically discuss the current evidence on gut microbiota-derived biomarkers of response and resistance to ICIs in HCC, with particular focus on microbial composition, microbiota-related metabolites, and emerging microbiome-based therapeutic strategies. This narrative review provides an updated overview of the role of gut microbiota as both a biomarker and a therapeutic target in patients with hepatocellular carcinoma (HCC) receiving immune checkpoint inhibitor (ICI) therapy. Full article

Infectious complications remain a principal determinant of late morbidity and mortality following major thermal injury, reflecting a convergence of barrier disruption, microbial adaptation, and host immune dysfunction. The post-burn environment creates a uniquely permissive niche for pathogen persistence, characterized by altered tissue perfusion, biofilm formation, and dynamic shifts in microbial ecology toward multidrug-resistant organisms. Concurrently, profound and evolving changes in host immunity and metabolism reshape both susceptibility to infection and response to therapy. This review integrates current evidence across pathophysiology, microbiology, diagnostics, and treatment, with a focus on challenges that limit effective infection control in burn patients. Particular attention is given to diagnostic uncertainty arising from overlap between sterile inflammation and true infection, the clinical implications of biofilm-associated tolerance, and the impact of burn-specific pharmacokinetic variability on antimicrobial efficacy. We further examine emerging diagnostic and therapeutic innovations, including host-response profiling, rapid molecular detection platforms, and next-generation anti-infective strategies targeting microbial virulence, biofilm structure, and host immune pathways. Despite substantial scientific advances, translation into clinical practice remains constrained by limited burn-specific trials, heterogeneous definitions, and systemic barriers to antimicrobial development. Collectively, these challenges underscore the need for integrated, precision-based approaches that combine early source control, individualized antimicrobial optimization, and advanced diagnostic frameworks. Future progress will depend on coordinated efforts to standardize definitions, generate high-quality multicenter data, and align innovation with clinical applicability across diverse healthcare settings. Full article

Background and Aim: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation. Environmental factors, including infectious agents, have been proposed to influence disease activity in inflammatory bowel disease. Although Borrelia burgdorferi has been shown to exert complex immunomodulatory effects on host immune responses, its seroprevalence and potential association with disease activity in patients with ulcerative colitis have not been systematically investigated. This study aimed to evaluate the seroprevalence of Borrelia burgdorferi IgG antibodies in patients with ulcerative colitis and to assess the relationship between seropositivity and laboratory markers of disease activity. Methods: In this retrospective observational study, 100 patients with ulcerative colitis (59 males, 41 females; mean age 48.5 ± 17 years) who underwent Borrelia burgdorferi IgG serological testing due to musculoskeletal or neurological symptoms suggestive of possible Lyme disease between October 2020 and October 2024 were included. Demographic characteristics, hematological and biochemical parameters, and inflammatory markers were compared between seropositive and seronegative groups. Due to the retrospective design, validated clinical disease activity indices were not consistently available; therefore, disease activity was indirectly assessed using laboratory inflammatory markers. Results: Among patients with ulcerative colitis, 22% were seropositive for Borrelia burgdorferi IgG. Seropositive patients had significantly lower uric acid, alkaline phosphatase, and C-reactive protein levels compared to seronegative patients (p = 0.001, p = 0.023, and p = 0.020, respectively). Free T4 levels were significantly higher in the seropositive group (p = 0.049). In terms of erythrocyte indices, mean corpuscular volume and mean corpuscular hemoglobin were significantly higher, while RDW-CV values were significantly lower in seropositive patients (all p < 0.05). Conclusion:Borrelia burgdorferi IgG seropositivity in patients with ulcerative colitis was associated with lower laboratory markers of systemic inflammation and a more stable hematological profile. Although causality cannot be established, these findings may suggest a potential association between prior Borrelia exposure and a distinct inflammatory phenotype in UC; however, this relationship should be interpreted with caution. Further prospective and mechanistic studies are warranted to clarify the potential immunological interactions between environmental microbial exposure and inflammatory bowel disease activity. Full article

Chandipura virus (CHPV) is a neurotropic rhabdovirus associated with recurrent outbreaks of acute encephalitis in children and a high case fatality rate, particularly in India. Despite its public health relevance, the host molecular processes governing CHPV infection and disease progression remain poorly defined. To address this gap, we conducted a time-resolved transcriptomic analysis to characterize host responses to CHPV infection and to explore host-directed therapeutic opportunities. Human HEK293T cells were infected with CHPV, followed by RNA sequencing (RNA-seq) at 6, 12, 18, and 24 h post infection (hpi). Transcriptome profiling revealed a temporally ordered host response. At 6 hpi, CHPV infection was dominated by strong activation of innate immune and inflammatory pathways, including interferon-stimulated genes and cytokine signaling. Antiviral responses persisted at 12 hpi, accompanied by suppression of metabolic and translational processes, indicating a shift in host cellular priorities. By 18 hpi, metabolic reprogramming—particularly involving lipid and sphingolipid metabolism—was observed alongside altered immune signaling, consistent with viral exploitation of host cellular machinery. At 24 hpi, repression of genes involved in chromatin organization, RNA processing, spliceosome assembly, and ribosome biogenesis reflected a global transcriptional shutdown associated with cytopathic effects. Integration of temporal transcriptomic signatures enabled identification of host pathways amenable to pharmacological targeting. Selected host-directed compounds were evaluated in vitro and exhibited antiviral activity against CHPV in a neuronal cell line. Collectively, this study provides the first time-resolved transcriptomic landscape of CHPV infection in human cells and identifies host-targeted strategies relevant for antiviral development. Full article

Inflammatory and autoimmune diseases are now understood to be significantly influenced by the intricate interactions between the microbiome and host physiology. This review investigates the function of epigenetic dysregulation in microbiome–host interaction and its consequences for health and disease. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNA-associated regulation, are key mechanisms that control gene expression without altering the underlying DNA sequence. Microbial metabolites and community composition alterations can cause disruptions in these epigenetic processes, resulting in dysregulated immune responses and the initiation of chronic inflammatory conditions. In particular, the diversity of gut microbiota alters host epigenetic patterns, affecting T cell differentiation, inflammatory modulation, and tissue homeostasis. Aberrant epigenetic modifications contribute to the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by promoting inflammation and autoimmunity. Similarly, gut microbiota dysbiosis has been implicated in the development and progression of inflammatory bowel disease (IBD). Identifying the reciprocal interaction between epigenetic alterations and microbiome dynamics provides unique insights into therapeutic options targeted at restoring microbial homeostasis to prevent disease progress. Consequently, understanding the intricacies of epigenetic dysregulation in microbiome–host interactions represents a significant sector in biomedical research and highlights the promise for precision medicine approaches in treating inflammatory and autoimmune diseases. The potential for microbiome-based therapies to affect host epigenetic landscapes requires additional research, paving the way for innovative therapeutic paradigms targeted at improving host resilience and restoring immunological balance. The purpose of this review is to synthesize current knowledge on how epigenetic dysregulation and microbiome–host interactions drive inflammatory and autoimmune diseases and to highlight emerging therapeutic opportunities. Full article

The autophagy regulator ATG7 helps maintain cellular homeostasis and has been suggested to modulate aspects of antiviral immune responses. In Drosophila, ATG7-dependent autophagy contributes to host resistance to vesicular stomatitis virus (VSV), a negative-strand RNA virus of family Rhabdoviridae that is widely used for studying viral biology and developing vaccines and virotherapy. However, the role of ATG7 in mammalian cells, especially non-immune cell types, remains unclear. Herein, we systematically examined the impact of ATG7 on VSV infection using CRISPR-edited cell lines derived from murine embryonic fibroblast (MEF), HeLa, and Huh7.5 cells, in relation to its effect on the expression of antiviral interferon-stimulated genes (ISGs). We found that ATG7 deficiency blocked basal as well as VSV-induced LC3B lipidation, concomitant with moderate reductions in progeny virus yields, while the reconstitution of ATG7 reversed the phenotypes. Mechanistically, ATG7 did not affect viral entry but rather was associated with moderate upregulation of VSV RNA replication. Intriguingly, ATG7 inhibited baseline ISG expression, and this correlated with its pro-VSV effect in all three cell types, while its suppression of innate immune responses elicited post-VSV infection did not. Altogether, these data provide new insights into the role of ATG7 in regulating VSV replication and innate immunity and have implications for developing VSV-based prophylaxis/therapeutics. Full article

Background: This case report presents a 12-year-old male with vertically transmitted chronic hepatitis B virus (HBV) infection, exhibiting a rare pan-reactive serological profile (concurrent HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb positivity) alongside fluctuating low-level viremia (HBV DNA: 1.06 × 10² IU/mL to undetectable). Rigorous exclusion of technical artifacts confirmed the authenticity of this atypical serologic pattern, observed in <0.001% of the general population. Methods: Liver biopsy and immunohistochemical staining were performed to evaluate hepatic inflammation and fibrosis. HBV serological markers and viral load were quantified using commercial diagnostic kits, with longitudinal monitoring for 18 months. Results: Liver biopsy revealed Grade 2 inflammation with focal HBsAg/HBcAg expression, supporting immune-active chronic hepatitis B (CHB) despite partial seroconversion. The patient’s clinical course highlights key challenges in pediatric HBV management: (1) delayed immune reconstitution (18-month longitudinal HBeAg/HBeAb dynamics), (2) non-linear virologic-ALT correlation, and (3) diagnostic ambiguity in pan-positive serology—potentially reflecting S-gene escape mutants or transitional immune responses. Initiation of tenofovir disoproxil fumarate (TDF) achieved sustained virologic suppression, underscoring the importance of early antiviral therapy in pediatric CHB with atypical markers. Conclusions: This case provides preliminary insights into the complex interplay between viral evolution and immature host immunity, advocating for refined monitoring protocols integrating high-sensitivity HBV DNA, quantitative serology, and non-invasive fibrosis assessment in pediatric HBV care. Full article

Understanding host cell response to viral infection could lead to the identification of molecular targets that can be used for the development of diagnostics and therapeutics. In this study, we investigated human dendritic cell (DC) response to infections with Vaccinia (VAC) virus, a highly immunogenic poxvirus, and Venezuelan Equine Encephalitis (VEE) virus, a single-stranded positive-strand RNA alphavirus, using human gene expression microarrays. Comparative changes in DC mRNA expression resulting from infection by the two viruses at 1, 8, and 12 h post-infection (hpi) revealed distinct temporal dynamics. VAC infection triggered early and robust activation of pathways related to chromatin organization, DNA damage, and antigen presentation, while VEE infection exhibited delayed activation of immune signaling pathways, including interferon signaling and cytokine production. Shared pathways, such as interferon signaling and inflammasome activation, highlight universal antiviral responses and potential therapeutic targets. These findings provide a molecular framework affected by VAC and VEE that need to be validated with additional experiments, such as functional assays or in vivo studies. The specific up- or downregulation of these pathways at different time points likely dictates the overall outcome of the viral infection and could potentially lead to better understanding of the temporal regulatory dynamics of virus host response. Full article