Search Results (44)

Dengue virus (DENV) remains a major global public health challenge, driven by the expanding distribution of Aedes vectors, rapid urbanization, and increasing climate variability. This review aimed to synthesize current evidence on dengue transmission dynamics, immunopathogenesis, molecular epidemiology, diagnostic and therapeutic advances, vaccine development, and the influence of climatic factors on disease patterns. A comprehensive search of major electronic databases was conducted to identify relevant literature, followed by a qualitative synthesis of the evidence. The evidence highlights complex transmission cycles involving Aedes aegypti and Aedes albopictus, with transmission strongly influenced by temperature, humidity, rainfall, and extreme climate events. Advances in immunopathogenesis research have improved understanding of mechanisms associated with severe disease, including antibody-dependent enhancement and dysregulated inflammatory responses. Diagnostic innovations, such as reverse transcription polymerase chain reaction (RT-PCR), NS1 antigen detection, and point-of-care technologies, have enhanced case identification, while prevention strategies increasingly incorporate integrated vector management, digital surveillance systems, and emerging vaccines. Integrating epidemiological, molecular, and climatic information may strengthen early warning systems, improve outbreak prediction, and support more effective dengue prevention and control strategies. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by substantial clinical and immunological heterogeneity. Once considered primarily a disorder of epidermal barrier dysfunction, AD is now recognized as a complex systemic inflammatory condition involving dysregulated immune responses, epithelial-derived signaling, neuroimmune interactions, and diverse molecular endotypes. Advances in molecular immunology have substantially improved understanding of the cytokine networks underlying disease pathogenesis and have accelerated the transition toward precision medicine approaches in AD. This narrative review summarizes current evidence regarding the immunopathogenesis of AD, focusing on the interplay between classical and emerging cytokine pathways, biomarker development, and recent therapeutic innovations. While interleukin (IL)-4 and IL-13 remain central drivers of type 2 inflammation and barrier impairment, additional mediators including IL-31, IL-33, IL-22, thymic stromal lymphopoietin (TSLP), and OX40/OX40L signaling, and the emerging Th9/IL-9 axis contribute to chronic inflammation, neuroimmune activation, epidermal remodeling, pruritus, and disease heterogeneity. Comparative evaluation of these pathways supports the identification of distinct immunological endotypes relevant to disease stratification and targeted therapy. The review further discusses current and emerging biomarkers associated with disease severity, therapeutic responsiveness, and inflammatory profiling, including cytokine signatures, serum biomarkers, and transcriptomic approaches. Recent advances in biologic therapies, Janus kinase (JAK) inhibitors, and novel cytokine-targeted interventions are discussed within the context of a precision medicine framework integrating immunological profiling, molecular endotyping, and mechanism-based therapeutic innovation. Continued advances in biomarker discovery, multi-omics technologies, and predictive therapeutic algorithms are expected to further refine disease stratification and support increasingly individualized management strategies for patients with AD. Full article

Inflammatory skin diseases are characterized by complex interactions between immune pathways, epidermal barrier function, and environmental triggers, leading to distinct clinical and histopathological features. This narrative review aims to integrate current knowledge on the cutaneous immune microenvironment across major inflammatory skin diseases, including atopic dermatitis, psoriasis, hidradenitis suppurativa, and vitiligo. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus, focusing on studies published between 2021 and early 2026. The findings highlight disease-specific immune signatures, such as Th2-driven inflammation in atopic dermatitis, IL-23/Th17 axis activation in psoriasis, neutrophil-dominated responses in hidradenitis suppurativa, and cytotoxic T-cell-mediated melanocyte destruction in vitiligo. These molecular pathways are closely reflected in histopathological patterns, emphasizing the link between morphology and immunopathogenesis. Advances in targeted therapies, including biologics and Janus kinase inhibitors, demonstrate the clinical relevance of these pathways and support a transition toward mechanism-based treatment strategies. Dermatopathology is increasingly contributing to precision medicine approaches by supporting correlations between tissue features, immune pathways, and potential therapeutic targets. This review provides a framework for improved disease stratification and for the development of personalized treatment strategies in inflammatory skin diseases. Full article

Food allergy is an exaggerated immune response, mediated by Immunoglobulin E (IgE) or by cells, to food antigens. Dogs and cats may present with both dermatological and gastrointestinal manifestations, although non-seasonal pruritus is the most common clinical sign. Despite advances in understanding the immunopathogenesis of this condition, the elimination–provocation test remains the gold standard for diagnosis. However, new diagnostic approaches, like molecular allergen macroarrays and lymphocyte proliferation assays, may complement traditional strategies, opening new perspectives for accurate diagnosis. For long-term management, strict avoidance of offending allergens is essential, but emerging therapeutic interventions, including immunotherapy using food components and targeted modulation of the gut–skin axis, are promising for improving clinical outcomes. This review summarizes current knowledge and highlights innovative approaches that can transform the diagnosis and management of food allergy in companion animals. Full article

Autoimmune ocular surface diseases represent a complex group of disorders in which systemic immune dysregulation triggers chronic inflammation, epithelial dysfunction, and progressive tissue fibrosis. Systemic lupus erythematosus, primary Sjögren’s syndrome, and ocular cicatricial pemphigoid are the principal entities linking systemic autoimmunity to ocular surface pathology. These conditions share convergent mechanisms—including dysregulated cytokine signaling (IFN-I, IL-6, and IL-17), complement activation, and epithelial–mesenchymal transition—culminating in tear film instability and visual impairment. Recent advances in molecular immunology and omics profiling have elucidated disease-specific pathways and identified actionable therapeutic targets. Conventional immunosuppressants such as corticosteroids and cyclosporine remain fundamental, yet emerging biologics targeting BAFF, IFNAR, and JAK/STAT signaling—alongside regenerative strategies employing mesenchymal and induced pluripotent stem cells—are transforming disease management. Parallel innovations in amniotic membrane transplantation, keratoprosthesis, and bioengineered corneal scaffolds integrate structural reconstruction with immune modulation. Furthermore, the convergence of multi-omics analytics, artificial intelligence-assisted diagnostics, and microbiome-based immunomodulation heralds a new era of precision ophthalmology. This review synthesizes current molecular insights, clinical observations, and translational advances that collectively redefine autoimmune ocular surface diseases—from chronic inflammatory disorders into a targetable, regenerative, and potentially reversible spectrum of conditions. Full article

Mycobacterium bovis is the causative agent of tuberculosis (TB) infecting a wide range of animal hosts, including humans. Domestic pigs (Sus scrofa domestica) are susceptible to different mycobacteria, particularly species within the Mycobacterium avium complex (MAC). However, in countries where bovine TB is endemic, such as Argentina, M. bovis is the most frequently reported species in pigs. This study aimed to evaluate the immune response and disease progression of a local strain (MB894) isolated from pigs and compare its pathogenicity with the highly virulent strain MB303, isolated from wild boar. Additionally, we sought to explore the genomic basis underlying the virulent phenotype of MB894. For this purpose, a murine infection model was used to assess pathogenicity, organ colonization, dissemination and cytokine induction. Whole-genome sequencing was performed to identify genetic features, including non-synonymous SNPs and INDELs, potentially associated with virulence. The severe immunopathogenesis produced by MB894, the higher multiplication rate in the evaluated organs, and the greater dissemination to other organs compared to MB303, combined with the cytokine levels induced by this strain, prompted us to classify MB894 as a hypervirulent strain. Genomic analysis revealed candidate genes that may be virulence factors contributing to this phenotype. In summary, MB894 represents a hypervirulent M. bovis strain with distinct pathogenic and genomic characteristics. These findings provide insights into the molecular determinants of virulence and highlight the need for further evaluation of identified gene candidates. Full article

Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system (CNS) that predominantly affects children and young adults. ADEM typically follows an infectious or, less commonly, immunization-related trigger, and despite decades of clinical observation, its etiopathogenesis remains only partially understood. Clinically, the diagnosis of ADEM continues to pose significant challenges due to the absence of disease-specific biomarkers and its clinical and radiological overlap with other acquired demyelinating syndromes. This narrative review aims to summarize and critically discuss current knowledge on ADEM, with particular emphasis on its etiopathogenesis and clinical characteristics, highlighting the potential implications of recent research for clinical practice and management of this disease. Particular emphasis is placed on post-infectious immune mechanisms, including molecular mimicry, blood–brain barrier (BBB) disruption, loss of immune tolerance, and neuroinflammatory cascades. A wide spectrum of infectious triggers—viral, bacterial, parasitic—as well as post-vaccination, post-transplantation, paraneoplastic, metabolic, and host-related genetic factors are discussed in the context of immune dysregulation leading to CNS demyelination. We also highlight characteristic clinical and neuroimaging features that may aid in differentiating ADEM from other demyelinating syndromes, while acknowledging current diagnostic limitations. The integration of recent advances in ADEM immunopathogenesis with established clinical and radiological insights underscores the complexity of this disorder and highlights the evolving nature of current concepts regarding its diagnosis and clinical heterogeneity. Full article

Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals, with a heterogeneous clinical spectrum spanning classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical forms. We synthesize contemporary epidemiology, immunopathogenesis, and the updated 2025 European Society for the Study of Coeliac Disease diagnostic framework. Adaptive responses to deamidated gliadin peptides presented by human leukocyte antigen (HLA)-DQ2/DQ8, together with interleukin-15-driven activation of intraepithelial lymphocytes (IELs), culminate in villous atrophy, crypt hyperplasia, and increased IELs. Serology centered on tissue transglutaminase immunoglobulin A (tTG-IgA) with total immunoglobulin A assessment remains first-line, complemented by standardized duodenal sampling (≥4 distal + 2 bulb biopsies) and selective HLA typing. The guidelines conditionally endorse a no-biopsy pathway for adults <45 years with tTG-IgA ≥10× upper limit of normal confirmed on a second sample, emphasizing shared decision-making and exclusion of red flags. We delineate differential diagnoses (tropical sprue, Crohn’s disease, common variable immunodeficiency, small intestinal bacterial overgrowth) and contrast CeD with non-celiac gluten sensitivity, which lacks villous atrophy, disease-specific serology, and HLA association. Emerging tools (immunohistochemistry, CD3/CD8/γδ IELs, video capsule endoscopy, confocal laser endomicroscopy) and the limitations of salivary/fecal assays are reviewed. Early detection improves quality of life and reduces healthcare utilization. Future directions include artificial intelligence-assisted imaging, molecular immunophenotyping, and non-dietary therapeutics. Full article

Chronic hepatitis C virus (HCV) infection remains a major global health burden, responsible for substantial morbidity and mortality despite the advent of curative antiviral therapy. HCV induces hepatic injury and carcinogenesis through direct viral effects, persistent inflammation, oxidative stress, and metabolic disturbance. The introduction of direct-acting antivirals (DAAs) has revolutionized therapy, achieving sustained virologic response rates exceeding 95% and transforming HCV from a chronic, progressive disease into a curable infection. Nevertheless, viral eradication does not fully normalize hepatic or systemic risk. Patients with advanced fibrosis or cirrhosis continue to face an elevated incidence of hepatocellular carcinoma (HCC) and other complications, reinforcing the need for long-term monitoring. This review summarizes current knowledge of the molecular mechanisms underlying HCV-mediated carcinogenesis, the partial restoration of hepatic homeostasis following DAA-induced cure, and the clinical implications for surveillance and management in the post-HCV era. By integrating insights from molecular virology, immunopathogenesis, and clinical hepatology, the review highlights how persistent epigenetic and inflammatory footprints may sustain oncogenic potential even after viral clearance. A comprehensive understanding of these processes is essential for optimizing HCC prevention strategies, guiding surveillance policies, and advancing future therapeutic innovations aimed at complete hepatic recovery. Full article

Background/Objectives: Cutaneous lupus erythematosus (CLE) is a complex autoimmune skin disease driven by genetic predisposition, environmental triggers, and immune dysregulation. Environmental factors such as ultraviolet radiation, smoking, and certain drugs can initiate disease onset by inducing keratinocyte apoptosis. The subsequent release of nucleic acids and danger-associated molecular patterns activates pattern recognition receptors (PRRs) on keratinocytes and immune cells, leading to the production of type I and type III interferons (IFNs) and pro-inflammatory cytokines. The objective of this review is to summarize recent advances in understanding the immunopathogenesis of CLE, with particular attention to emerging cellular players and their therapeutic implications. Methods: A narrative review of the recent literature was performed, including experimental, translational, and clinical studies investigating the cellular and molecular mechanisms underlying CLE and novel targeted treatments derived from these findings. Results: Although plasmacytoid dendritic cells (pDCs) have traditionally been considered the major producers of IFN-I, recent data indicate that pDCs in CLE are functionally impaired and are not the primary source. Other cells, such as keratinocytes have emerged as key producers of IFN-I, contributing to a prelesional, IFN-rich microenvironment. This promotes the recruitment and activation of dendritic cells and other inflammatory myeloid subsets, which are now recognized as central players in amplifying local inflammation. Concurrently, T cells infiltrate the skin, where cytotoxic CD8⁺ T cells attack keratinocytes and CD4⁺ T cells further propagate inflammation via cytokine production. B cells and plasma cells produce autoantibodies, forming immune complexes that perpetuate inflammation. Neutrophils release neutrophil extracellular traps (NETs), exposing autoantigens and further stimulating IFN pathways. Macrophages contribute by presenting autoantigens, producing pro-inflammatory mediators, and failing to effectively clear apoptotic cells and immune complexes. Conclusions: The dynamic interplay between the innate and adaptive immune systems sustains the chronic inflammatory state characteristic of CLE. Based on the pathogenetic novelties, new therapeutic agents targeting specific molecules have been developed, which may improve the treatment of this complex disease in the future. Full article

Canine atopic dermatitis (cAD) is a chronic, pruritic, inflammatory skin disease with complex immunopathogenesis involving dysregulated cytokine networks. In recent years, targeted therapies have transformed the management of cAD by directly or indirectly modulating cytokine activity. Lokivetmab, a monoclonal antibody neutralizing interleukin-31, represents a breakthrough in veterinary dermatology, providing rapid and sustained reduction in pruritus with a favorable safety profile. Janus kinase inhibitors, including oclacitinib and the newer ilunocitinib, act downstream by blocking cytokine signal transduction, offering effective control of both acute and chronic phases of disease. Ciclosporin, a calcineurin inhibitor, remains a valuable immunosuppressant for long-term cAD management, while topical tacrolimus provides localized benefits. Together, these therapies mark a paradigm shift from non-specific immunosuppressants to precision medicine. In this context, precision medicine refers to therapeutic strategies that selectively target key cytokines or intracellular signaling pathways central to the pathogenesis of cAD, such as IL-31 or the JAK/STAT axis. Unlike traditional immunosuppressants such as glucocorticoids, which exert broad and non-selective immune suppression, these agents modulate defined molecular mechanisms, thereby improving efficacy and minimizing adverse effects. Consequently, they enable improved quality of life for affected dogs and their owners. Future strategies will likely focus on patient stratification and personalized approaches based on immunological endotypes. Full article

Systemic lupus erythematosus is a multifactorial autoimmune disease characterized by the dysregulation of both innate and adaptive immunity, resulting in chronic inflammation, autoantibody production, and multi-organ damage. Innate immune dysfunction involves macrophages, neutrophils, plasmacytoid dendritic cells, natural killer cells, and the complement system, which collectively amplify autoimmunity through defective clearance of apoptotic cells, overproduction of pro-inflammatory cytokines, and abnormal type I interferon signaling. Adaptive immune abnormalities, including skewed T-cell subsets, impaired regulatory T and B cells, and autoreactive B-cell hyperactivity, further perpetuate pathogenic autoantibody generation. Gut microbiota dysbiosis contributes to SLE pathogenesis via Th17 activation, loss of mucosal tolerance, and molecular mimicry mechanisms. This review synthesizes current knowledge on the immunopathogenesis of SLE, emphasizing the interplay between innate and adaptive immunity and integrating evidence from both human and experimental murine models to provide a comprehensive understanding of disease mechanisms. Full article

Dry eye disease (DED) is increasingly recognized as a condition driven by immune dysregulation at the ocular surface (OS). Chronic inflammation, mediated by aberrant activation of both innate and adaptive immune pathways, underlies disease progression and symptom persistence. Neuroimmune interactions further amplify OS inflammation, contributing to epithelial damage and impaired homeostatic regulation. This review summarizes current literature on the immunopathogenesis of DED, highlighting the complex interplay of molecular mechanisms of innate and adaptive immune activation, neuroimmune-mediated inflammation, and emerging molecular and cellular biomarkers. In addition, we examine existing and emerging therapeutic strategies that target these immune-molecular pathways, including precision immunomodulatory approaches, to inform future management of DED. By integrating mechanistic insights with clinical findings, this review aims to provide a comprehensive overview of the molecular mechanisms underlying the dysregulated immune response associated with DED. Full article

Insect bite hypersensitivity (IBH) is a seasonally recurrent allergic dermatitis representing one of the most prevalent dermatological conditions in horses worldwide. This condition, driven by hypersensitivity to salivary allergens of Culicoides spp., causes substantial discomfort, welfare impairment, and potentially economic loss in equine populations. The pathogenesis of IBH is complex, involving genetic predisposition, epithelial barrier dysfunction, and a skewed T-helper 2 (Th2)-mediated immune response with elevated IgE production and eosinophilic inflammation. Advances in immunogenetics and molecular immunology have improved the understanding of the disease’s multifactorial nature. Research on immunotherapy and cytokine-targeted treatments is contributing to the development of more effective therapeutic options. This review synthesizes current knowledge on the immunopathogenesis and genetic determinants of IBH and discusses both conventional and emerging strategies for its clinical management. Full article

Alternaria alternata is one of the most clinically relevant fungal allergens in pediatric patients with respiratory allergies. Sensitization to this mold has increased in recent decades and is influenced by environmental exposure, geographic location, climate change, and genetic predisposition. In children, Alternaria spp. are strongly associated with the development and worsening of asthma and allergic rhinitis, often contributing to severe and difficult-to-control forms of the disease. The major allergen, Alt a 1, plays a central role in the immunopathogenesis of Alternaria-induced allergies and exhibits molecular features that allow cross-reactivity with other fungal species. Although Alternaria allergy is clinically relevant, its diagnosis remains challenging due to the variability and lack of standardization of fungal extracts. Therefore, it may be necessary to complement traditional diagnostic tools, such as skin prick testing and specific IgE measurement, with component-resolved diagnostics or, in selected cases, nasal provocation tests. Allergen immunotherapy (AIT) has shown promising results in the treatment of Alternaria allergy, particularly with the use of standardized Alt a 1-based extracts or chemically modified allergoids, which offer clinical benefits and immunological modulation. However, AIT is still underused in this context, partly because of the lack of widely available commercial products and long-term efficacy data in the pediatric population. This review provides a comprehensive overview of the current knowledge on the epidemiology, mechanisms, clinical implications, and treatment options related to Alternaria allergy in children, with the aim of supporting early recognition and tailored therapeutic strategies for this important, yet often underestimated, allergen. Full article