Search Results (362)

Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis vaccines that contribute to ongoing transmission. A narrative review of the literature was conducted, focusing on mechanisms of host–pathogen interaction, immune evasion, and vaccine-induced immunity. Evidence indicates that although acellular vaccines effectively reduce disease severity, they fail to prevent nasopharyngeal colonization and transmission, largely due to insufficient induction of mucosal immunity, T helper 1 (Th1) and T helper 17 (Th17) responses, and airway tissue-resident memory T cells. In contrast, natural infection induces broader immune responses, including secretory IgA production and robust cellular immunity, which are associated with improved bacterial clearance. Emerging next-generation vaccine strategies, including mucosal, outer membrane vesicle-based, and live-attenuated platforms, demonstrate enhanced ability to reduce bacterial colonization in preclinical and clinical models. In conclusion, effective control of pertussis transmission will require vaccine approaches that replicate infection-induced immunity at the respiratory mucosa, emphasizing the need for redesigned immunization strategies. Full article

Hormonal fluctuations across female life stages drive numerous transcriptomic and epigenetic changes, yet the effects of sex hormones on mucosal immunity, particularly in the vaginal epithelium, remain poorly understood. The vaginal mucosa undergoes cyclical remodeling during the ovulatory cycle under the influence of estrogens and progesterone produced mainly in the ovary. The ovary can also be a source of testosterone, and in postmenopausal women, as well as transgender men receiving hormone therapy, phenotypic changes in the vagina due to increased testosterone have been observed. However, the consequences of testosterone dominance in this tissue in terms of resilience and inflammation have not been well characterized. The goal of this study was to identify the histological and immunological changes within the vaginal epithelial cell barrier in an estrogen- vs. testosterone-dominant environment using an established in vitro reconstructed vaginal epithelial tissue model. Compared to estradiol, exposure to testosterone resulted in a thinner tissue with alterations in the cornification, although no impairment in the epithelial barrier was detected. Each hormone also resulted in a unique RNA expression profile, including increased expression of tight junction genes and decreased expression of chemokines and their receptors in testosterone compared to estradiol exposure. These data have implications for women’s health, including menopause, transgender men using gender-affirming hormone therapy, and other conditions associated with high testosterone in the vaginal compartment. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation, synovial hyperplasia, and progressive joint destruction. Periodontitis, a chronic inflammatory disease affecting the supporting structures of teeth, has been increasingly recognized as a potential contributor to RA pathogenesis. Evidence suggests that both conditions share common immunological mechanisms and microbial triggers. This review summarizes the data linking RA with periodontitis, with particular focus on shared pathogenic pathways, microbial triggers, immune system alterations, and clinical relevance. Methods: Experimental, epidemiological, and clinical studies were evaluated to explore biological and clinical links between periodontitis and RA. Special emphasis was placed on the mucosal origins of RA, bacterial-mediated citrullination, autoantibody formation, and the role of the complement system. Results: Available epidemiological data indicate that individuals with RA present higher prevalence and greater severity of periodontitis. Periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, contribute to immune dysregulation through citrullination, and subsequent production of anti-citrullinated protein antibodies (ACPAs), a hallmark of RA. Both diseases are characterized by chronic, uncontrolled inflammation, amplified by complement activation and neutrophil hyperactivity. Clinical evidence suggests that non-surgical periodontal therapy may reduce systemic inflammatory markers and improve RA disease activity. Conclusions: The relationship between RA and periodontitis appears to be bidirectional and the recognition of this interaction supports closer collaboration between rheumatologists and dental professionals. Future studies are required to clarify causality and determine whether management strategies can influence patient outcomes. Full article

Background: Infectious hematopoietic necrosis virus (IHNV), a rhabdovirus classified within the genus Novirhabdovirus, continues to be one of the most detrimental pathogens impacting salmonid aquaculture on a global scale. Notable for inducing high mortality rates among fry and fingerlings, IHNV represents a substantial threat to the economic stability of the aquaculture industry. This review offers an in-depth analysis of the contemporary advancements in IHNV vaccine development. Methods: We assess the efficacy and immunological mechanisms of traditional vaccine platforms, including inactivated and live-attenuated vaccines, while emphasizing the groundbreaking success of DNA vaccines, particularly those encoding the viral glycoprotein (G). Although nucleic acid-based therapies provide high levels of protection, they face logistical challenges related to delivery and regulatory obstacles associated with Genetically Modified Organisms (GMOs). Additionally, we examine emerging “next-generation” platforms, such as viral vector vaccines, subunit proteins produced in yeast or plant systems, and RNA-based technologies. We critically analyze technical bottlenecks, including the lack of efficient mucosal delivery systems and the limited understanding of long-term cellular memory in teleosts. Results: We propose future research directions that emphasize the development of multivalent formulations and the incorporation of molecular adjuvants to augment mucosal immunity. Conclusions: This synthesis seeks to integrate fundamental viral pathogenesis with applied immunology to develop a strategic framework for the sustainable, long-term management of IHNV in global salmonid populations. Full article

Viral infections with gastrointestinal involvement remain a significant global health burden with limited therapeutic options. While probiotics show antiviral potential, their impact on primary human intestinal epithelial defenses is poorly defined. This study utilized human intestinal organoid-derived monolayers (ODMs), generated from the non-inflamed mucosa of patients with inflammatory bowel disease, to examine how Bifidobacterium animalis ssp. lactis BB-12 (BB-12) and Lacticaseibacillus rhamnosus GG (LGG) modulate mucosal antiviral pathways. Unlike conventional Caco-2 cells, ODMs preserved physiological cellular diversity and intact innate signaling. Expression of viral receptors and interferon (IFN)-stimulated genes (ISGs) was quantified by RT-qPCR, while the effector 2′-5′-oligoadenylate synthetase 1 (OAS1) was also assessed by immunofluorescence and flow cytometry. Both probiotic strains modulated IFN-associated pathways; however, BB-12 induced a markedly stronger antiviral transcriptional response than LGG. Notably, OAS1 exhibited cell type-specific regulation; while goblet cells showed high basal levels, both probiotics enhanced OAS1 expression selectively in ileal enterocytes. Despite this shared effect, only BB-12 pretreatment significantly restricted Influenza A (H1N1) replication in ileal ODMs, whereas LGG did not significantly affect viral replication. These findings establish human ODMs as a superior platform for probiotic immunology, suggesting that BB-12 more effectively shapes epithelial antiviral “set-points” and highlighting OAS1 as a sensitive component of a broader antiviral program. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective treatments for obesity, but substantial weight regain is common after therapy is discontinued. This study investigated whether probiotic strains with anti-obesity effects could enhance GLP-1RA-induced weight loss and attenuate post-treatment weight rebound. Methods: Candidate lactic acid bacteria were screened for anti-obesity efficacy in a high-fat-diet (HFD)-induced obese mouse model, and the selected strain was further characterized using metabolomic profiling of culture supernatants. To examine its interaction with GLP-1RA therapy, obese mice received dulaglutide for 4 weeks and were monitored for 2 weeks after treatment withdrawal, while the probiotic was orally administered for a total of 6 weeks. Body weight, glycemic parameters, and muscle strength were assessed throughout the study. Results: Limosilactobacillus fermentum GB102 reduced body weight and improved glycemic control in HFD-fed mice. These metabolic benefits were associated with alterations in circulating metabolic hormones, including adipokines, along with attenuated inflammatory responses in adipose tissue. Metabolomic profiling revealed that GB102 produced high levels of succinic acid, a metabolite previously linked to thermogenic activation. This strain increased whole-body energy expenditure in HFD-fed mice, produced glutamine, and showed enhanced conversion of arginine into ornithine and citrulline. When combined with dulaglutide, GB102 enhanced weight loss, preserved muscle strength, and attenuated both weight regain and glycemic rebound following dulaglutide withdrawal. Conclusions: These findings suggest that energy-metabolism-enhancing probiotics such as GB102 may enhance the metabolic effects of GLP-1RA therapy and help attenuate weight regain after treatment discontinuation. Full article

Vitamin D is a pleiotropic secosteroid with endocrine and intracrine actions that influence key phases of allogeneic hematopoietic stem cell transplantation. Epithelial barriers, antigen-presenting cells and effector lymphocytes express the vitamin D receptor and enzymes required for local activation, allowing circulating 25-hydroxyvitamin D to be converted into its active form and modulate immune interactions. During the peri-transplant period, sunlight deprivation, reduced intake, mucosal injury, cholestasis and corticosteroid exposure markedly reduce vitamin D levels at a time when antigen presentation and immune reconstitution occur. This review integrates mechanistic immunology with clinical observations and interventional data to outline strategies that prevent severe deficiency. It summarizes epidemiology before and after transplantation, associations with acute and chronic graft-versus-host disease, relapse, engraftment, infections, bone health and survival, and evaluates dosing approaches including pre-conditioning loading and reassessment at day thirty with escalation if needed. Absorption-savvy formulations such as oral thin-film and intramuscular cholecalciferol are considered when gastrointestinal function is compromised. Given the high prevalence of deficiency, biological plausibility, safety and low cost, a structured approach that includes screening, repletion and monitoring to achieve concentrations of at least thirty nanograms per milliliter by day thirty represents a pragmatic and low-risk component of supportive care pending definitive evidence. Full article

Candida fungi are among the most common human fungal pathogens and invasive candidiasis is one of the predominant invasive mycoses that mainly affects hospitalized patients with suppression of the immunological system and breaches in skin or mucosal barriers. Rapid diagnosis and implementation of appropriate antifungal treatment are key to achieving recovery. In recent years, attention has been drawn to the increasing significance of Candida species other than C. albicans, in particular C. auris and fluconazole-resistant C. parapsilosis. The aim of this work was to present the species spectrum and drug susceptibility of 570 Candida strains isolated from candidemia cases diagnosed in patients hospitalized in southern Poland in the period 2017–2022. The results of Candida-positive blood cultures obtained from five hospitals were analyzed. C. albicans was the most common species, accounting for 42.6% of all strains, followed by Nakaseomyces glabratus (formerly C. glabrata) and C. parapsilosis complex—22.1% and 18.8%, respectively. No C. auris was found. Fluconazole resistance was found in 4.9% of C. albicans strains, 34.7% of N. glabratus strains, and 8.7% of C. parapsilosis complex strains. Full article

Swine influenza virus (SIV) continues to evolve and possesses notable zoonotic potential, making it an important respiratory pathogen of concern for both the global swine industry and public health. Owing to antigenic drift, genetic reassortment, and regional lineage diversity, vaccine efficacy against SIV shows marked variability across different epidemiological contexts. Therefore, establishing appropriate animal models to dissect its pathogenic mechanisms, transmission characteristics, and immune response patterns is of critical importance. This review systematically summarises the animal models commonly used in SIV research, including mice, ferrets, guinea pigs, pigs, and non-human primates, and provides an integrated analysis across three core dimensions: pathological manifestations, viral replication kinetics, and immune architecture. The evidence indicates that substantial inter-model differences exist in pulmonary lesion distribution, transmission efficiency, mucosal immune development, and cellular immune complexity, which in turn define their functional roles in mechanistic studies, transmission research, and vaccine evaluation. Building on this framework, this review further emphasises the value of a tiered, multi-model strategy in SIV research. In vitro systems and mouse models are well suited for early mechanistic exploration and preliminary vaccine screening; ferret and guinea pig models facilitate the evaluation of transmission dynamics; and the pig model, as the natural host system, remains the critical platform for confirming protective efficacy, identifying potential immunopathological risks, and assessing translational relevance. Importantly, the potential occurrence of vaccine-associated enhanced respiratory disease under antigen-mismatched conditions highlights the need to evaluate both protective performance and immunological safety during vaccine development. Overall, rational integration of evidence across multiple models, anchored to the natural host, will improve the predictability and translational reliability of SIV vaccine research. Full article

Human breast milk evolves beyond simple nutrition to function as a complex signaling system that promotes neonatal development. This review analyzes the bioactive components, delineating how its specific constituents compensate for the physiological vulnerabilities of the neonate. Additionally, the distinct roles of colostral and mature milk are in fortifying the immature immune system and promoting gastrointestinal maturation. Focus is placed on the prevention of necrotizing enterocolitis, where milk oligosaccharides and microbiome function to maintain mucosal integrity and symbiosis, while preventing pathogens’ adhesion. Furthermore, how breastfeeding duration is linked to long-term metabolic and immunological programming is evaluated. MicroRNAs and bioactive lipids actively modulate gene expression and immune responses, thereby reducing the incidence of metabolic diseases and childhood malignancies. By integrating findings, this article underscores the irreplaceable role of breast milk in clinical dietetics and pediatric care. Full article

Background: Members of the virus family Herpesviridae are among the most successful pathogen groups in evolutionary history. They not only pose a serious public health threat to humans but also cause significant economic losses in the global livestock industry. The primary immunological challenge in developing sterilizing vaccines is the lifelong latency of herpesviruses in the nervous system or lymphoid tissues. Methods: This analysis compares the vaccine strategies designed against the five most important Alphaherpesvirinae pathogens: HSV-1/2, PRV, BHV-1, EHV-1/4, and FHV-1. The contrast between the globally licensed veterinary vaccines and the relative stagnation in the field of human HSV vaccines is stark. However, there are notable success stories regarding the implementation of ‘Marker Vaccines’ (DIVA strategies) in veterinary medicine. This review examines various vaccine modalities, assessing their potential to mitigate clinical outbreaks and their shortcomings in preventing viral shedding and establishing latency. Results: This study reveals common technical bottlenecks across species, attributed to immune evasion mechanisms such as the downregulation of MHC I, TAP inhibition, the failure to induce robust mucosal IgA, and safety concerns regarding the recombination of live vectors. Conclusions: This review highlights several promising avenues that could lead to enhanced herpesvirus vaccines and recommends the rational design of T-cell epitopes alongside innovative mucosal adjuvants. Furthermore, it bridges the gap between veterinary and human vaccinology from a One Health perspective, suggesting that lessons learned from veterinary practices could facilitate necessary breakthroughs in human medicine. Full article

Postbiotics produced by beneficial bacteria are emerging as safe dietary approaches to intestinal inflammation. We evaluated intestinal bacterial metabolites (IBM), a cell-free fermented soybean extract generated by co-culturing 31 Lactobacillus/Bifidobacterium-related strains, for prophylactic protection in 3% dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6NJ mice received oral IBM (0.4 or 2 mL/kg/day) or vehicle for 7 days before and during 7 days of DSS. Disease activity index (DAI), colon length, and histopathology were assessed, and endpoint serum cytokines were quantified by a multiplex bead assay. DSS-independent responses were examined in healthy mice after 7 days of IBM by rectal RNA sequencing and cecal 16S rDNA profiling, and direct epithelial effects were tested in HCT-116 and DLD-1 cells treated with 2% IBM. IBM attenuated colitis, improving DAI, preventing colon shortening, and ameliorating histopathology, with decreased IL-23 and IL-17A and increased IFN-β and GM-CSF. Rectal transcriptomics showed modulation of circadian programs, upregulation of mucosal/barrier genes, and reduced extracellular-matrix remodeling signatures. IBM increased junctional proteins and barrier-related transcripts in vitro and shifted the microbiota, increasing Lactobacillus and Roseburia while decreasing Streptococcus and Staphylococcus. These coordinated clinical, immunological, transcriptomic, epithelial, and microbiome changes support prophylactic protection by IBM against DSS colitis. Full article

Background/Objectives: Pregnancy loss is a common and multifactorial complication of human reproduction, traditionally attributed to fetal chromosomal abnormalities, maternal anatomical and endocrine disorders, and immune dysfunction. Growing evidence now indicates that the maternal microbiome, particularly within the reproductive tract, plays a critical role in implantation, placental development, and the maintenance of immune tolerance during early pregnancy. Importantly, the influence of the microbiome on miscarriage appears to be strongly modulated by host genetic background and immune regulation. Methods: This narrative review summarizes current evidence linking alterations in the vaginal, endometrial, placental, and gut microbiomes to miscarriage, with a specific focus on host genetics and immune–microbial interactions. Results: We discuss how genetic variation in innate and adaptive immune pathways, inflammatory signaling, and mucosal barrier function may shape host responses to microbial communities, thereby influencing susceptibility to PL. In addition, we highlight emerging data on microbiome-driven regulation of gene expression and epigenetic modifications in the endometrium and decidua, emphasizing the role of microbial metabolites in immune tolerance and placental function. Conclusions: By integrating findings from microbiome research, host genomics, immunology, and epigenetics, this review proposes a framework in which miscarriage is viewed as a consequence of disrupted host–microbe crosstalk rather than isolated pathology. Finally, we address key methodological challenges and outline future research directions aimed at advancing mechanistic understanding and translational applications. Full article

Background/Objectives: Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, potentially fatal immunological conditions that affect cutaneous and mucosal surfaces and have the potential to involve the genitourinary tract. While genital involvement is common, urological manifestations are under-recognised clinically and there is a paucity of clear, evidence-based management pathways specific to urological manifestations of SJS/TEN. To map the spectrum of urological manifestations of SJS/TEN, to describe the short- and long-term outcomes of these manifestations, and to synthesise management and prevention strategies to inform clinical practice. Methods: This was a scoping review conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guideline. Data sources: Medline and PubMed articles published in English with publication date up to December 2025. Study selection: Eligible studies included case reports, case series, observational studies, clinical guidelines, and review articles describing urological manifestations, outcomes, management, or prevention strategies for patients with SJS/TEN. Articles limited to renal or isolated gynaecological involvement were excluded. Data extraction and synthesis: Articles were screened independently by two reviewers using a pre-defined data extraction template covering four domains: urological manifestations, outcomes and sequelae, management strategies, and prevention strategies. This criterion was refined after a pilot of 20 studies. Discrepancies were resolved by consensus with a third reviewer. Formal risk-of-bias assessment was not performed, consistent with scoping review methodology. Results: One hundred and four studies published between 1987 and 2025 were included in this review. Selected articles included case reports (n = 63), retrospective cohort studies (n = 23), prospective studies (n = 2), guidelines (n = 5), and summary articles (n = 11). Reported urological involvement ranged from genital cutaneous and mucosal disease including erosions, adhesions, and balanitis to urethral manifestations such as urethritis, stenosis, and strictures, as well as scarce upper urinary tract involvement including ureteric stricture and ureteric mucosal sloughing. While some manifestations resolved with supportive care, others progressed to chronic sequelae including persistent urethral strictures, voiding dysfunction, sexual dysfunction, recurrent infection, and in rare cases, obstructive uropathy. A multidisciplinary approach was recommended for all patients with SJS/TEN. Urological management centred around early and repeated urogenital examination, manual lysis of adhesions, urinary catheterisation, and timely intervention for urethral or ureteric obstruction. Long-term urological follow-up of 12 months was recommended for patients with significant urogenital involvement. Conclusions: Urological manifestations of SJS/TEN are diverse, clinically significant, and frequently under-recognised. Early urological involvement, systematic genital and urinary tract assessment, and proactive preventative measures may reduce long-term morbidity. This review provides a comprehensive synthesis of knowledge and recommendations to support urologists’ role in multidisciplinary care of patients with this pathology. This review also highlights the need for prospective research to guide further evidence-based management of urological complications of SJS/TEN. Full article

Live attenuated Salmonella enterica serovar Typhimurium has been investigated for decades as an orally delivered vaccine vector due to its ability to target the intestinal mucosa and engage both innate and adaptive immune responses. In humans, S. Typhimurium infection is largely restricted to the gastrointestinal tract, distinguishing it from Salmonella Typhi and providing a rationale for its use in mucosal vaccine strategies. In this review, we discuss the biological features of S. Typhimurium that support its use as a vaccine vector and summarize current understanding of the immune responses generated during wild-type infection, including innate activation and downstream T cell and B cell responses. We compare key biological differences between Salmonella Typhi and S. Typhimurium and outline emerging vector design strategies, including delayed attenuation and chromosomal integration of heterologous antigens. We then review applications of attenuated S. Typhimurium vectors targeting viral, bacterial, and parasitic pathogens, highlighting shared immunological outcomes and design principles across platforms. Finally, we discuss recent advances in vector engineering, including chromosomal integration of heterologous antigens, as well as remaining gaps in knowledge related to the durability of immune responses and translational considerations. Full article