Search Results (7,285)

Osseointegration is the direct contact between living bone and a dental implant, with supporting evidence confirming the direct connection between bone and titanium, found using an electron microscope. However, the fundamental mechanisms and interconnections between the bone and titanium are not clearly understood. At present, osteoimmunology explores the interaction between bone and immune cells not only in the medical field but also in dentistry. Immunology in bone cell formation has long been a research topic; however, interest in these effects has recently surged. Through subsequent studies, osteoimmune reaction occurs in response to dental implant insertion into the bone and this mechanism portrays more accurate tissue response compared to the traditional term osseointegration. Additionally, osseointegration is a foreign body defense mechanism to protect the implant when bone forms at the contact surface between the dental implant and the alveolar bone. The term “osteoimmunology” refers to the relationship between the immune system and bone tissues. Understanding osteoimmunologic concepts may enable the development of immunomodulatory strategies to improve, maintain, and ultimately restore osseointegration. In order for biocompatible materials such as dental implants to settle and be maintained in the body, it is necessary to understand the complex interrelationships of the bone immune environment, which will enable the development of biomaterials that are more favorable to osteoimmune environments. Therefore, this review presents previous insights into cellular and molecular interactions between bone and the immune system, specifies the roles of T-regulatory cells (Tregs) and macrophages, and demonstrates their potential for translational applications worldwide. Full article

The behavioral immune system (BIS) refers to a set of evolved psychological mechanisms designed to detect cues of potential pathogen threat and trigger self-protective, avoidant behaviors. However, like all adaptations, the BIS carries potential costs alongside its benefits. This study aimed to examine the impact of BIS-related processes on mental health outcomes—including depression, anxiety, stress, and obsessive–compulsive symptomatology—during the COVID-19 pandemic. Data were collected online at two time points: the onset of the pandemic (May 2020; n = 990; 86% women) and at the end of its first year (November/December 2020; a subsample of the original participants, n = 182). Hierarchical regression analyses were conducted, entering socioeconomic variables and general quality of life in the first block, followed by BIS-related variables (germ aversion and perceived infectability) in the second block. Results showed that socioeconomic status and general quality of life were significant predictors of mental health difficulties at both time points, consistent with prior findings on the harmful effects of environmental and social stressors. Importantly, BIS variables also emerged as significant and independent predictors of mental health outcomes—including the development of obsessive–compulsive symptoms—highlighting the potential psychological costs of pathogen-avoidant motivations governed by the BIS. Full article

Congenital Rubella Syndrome (CRS) results from maternal infection with the rubella virus during pregnancy, particularly in the first trimester, when the risk of vertical transmission and severe fetal damage is highest. CRS is characterized by a broad spectrum of congenital anomalies, including sensorineural hearing loss, congenital heart defects, cataracts, neurodevelopmental delay, and behavioral disorders. Despite the absence of specific antiviral therapies, active immunization remains the only effective strategy to prevent rubella infection and its congenital consequences. Global immunization efforts, particularly in the Americas, have led to the elimination of rubella and CRS in several countries. However, challenges persist in the post-elimination era, including declining vaccine coverage, vaccine hesitancy, and setbacks caused by the COVID-19 pandemic. Diagnosis relies on maternal serology, fetal imaging, postnatal antibody testing, and molecular techniques. Management requires long-term, multidisciplinary follow-up due to the complex and lifelong sequelae affecting sensory, motor, and cognitive development. This review highlights the clinical, epidemiological, and pathophysiological aspects of CRS, while emphasizing the urgent need to maintain high vaccination coverage and strengthen surveillance systems. Sustained public health commitment is essential to prevent the reemergence of rubella and protect future generations from this preventable syndrome. Full article

Natural autoantibodies (nAAbs) recognize self-antigens and are an important component of the immune system, having evolved from invertebrates to vertebrates, and are viewed as stable byproducts of immune function and essential players in health and disease. Initially characterized by their conserved nature and multi-reactivity, primarily as IgM isotypes, nAAbs are now recognized for their adaptability in response to infections and vaccinations, bridging innate and adaptive immunity. The nAAbs and the cellular elements, such as γδ T, iNKT, and MAIT cells, of the natural immune system perform a primary defense network with moderate antigen-specificity. This comprehensive literature review was conducted to analyze the role of natural autoantibodies (nAAbs) in health and disease. The review focused on research published over the past 40 years, emphasizing studies related to infectious diseases, vaccinations, and autoimmune disorders. Recent studies suggest that nAAbs engage in complex interactions in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and type 1 diabetes. Their roles in immunological processes, such as maternal tolerance during pregnancy, further underscore their complexity. Emerging evidence indicates that nAAbs and the cellular elements of the natural immune system may contribute to both disease pathogenesis and protective mechanisms, highlighting their dual nature. Continued research on nAAbs is vital for improving our understanding of immune responses and developing therapeutic strategies for autoimmune disorders and infectious diseases. Full article

Fowl adenovirus can cause various diseases such as hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH), which leads to huge economic losses for China’s poultry industry. In recent years, the prevalence of FAdV-4, FAdV-8a, and FAdV-8b has been on the rise. In this study, a trivalent fowl adenovirus inactivated vaccine against FAdV-4/8a/8b was generated and the immune effect was evaluated. The results showed that chickens immunized with the trivalent vaccine could effectively resist the challenge of virulent strains of FAdV-4, FAdV-8a, and FAdV-8b. All chickens in the immunized groups survived after virus injection, gained weight normally, and the lesions in tissues and organs (liver, spleen, kidney, etc.) were significantly decreased compared with the control group. The viral load in the liver of the immunized group was significantly lower than that of the challenge control group five days after the challenge (p < 0.01), and the cloacal excretion was significantly lower than that of the non-immune control group (p < 0.01). Moreover, until 16 weeks after immunization, the neutralizing antibody level against FAdV-4, FAdV-8a, and FAdV-8b remained above 8.27 log2. As a result, the trivalent vaccine generated in our study was an attractive candidate to prevent and reduce the spread of HHS and IBH in China’s poultry industry. Full article

Background Psoriasis (PsO): is an immune-mediated inflammatory disease that imposes a significant burden on patients. Many patients experience relapse or inadequate responses, and PsO subtypes also lack effective therapies, highlighting the need for new therapeutic targets. Methods: We performed a proteome-wide Mendelian randomization (MR) to explore potential therapeutic targets for PsO. Protein quantitative trait loci (pQTLs) data were obtained from the Pharma Proteomics Project (54,219 UK Biobank participants, 2923 proteins), and PsO phenotype and subtype data were sourced from FinnGen (10,312 cases; 397,564 controls) for discovery. Replication MR utilized integrated protein data (Iceland and Norfolk) and phenotype data from multiple databases (UK Biobank and GWAS Catalog). Reverse MR and colocalization were used to support causal relationships. Single-cell RNA-seq analysis revealed distinct expression patterns of protein-coding genes across different cell types in PsO biopsy samples and normal skin tissues. Protein-protein interactions (PPI) and molecular docking were used to evaluate druggability. Results: MR analysis identified 13 proteins significantly associated with PsO risk (p < ), including 10 proteins associated with PsO subtypes. Decreased levels of eight proteins (IFNLR1, APOF, TDRKH, DDR1, HLA-E, LTA, MOG, and ICAM3) and increased levels of five proteins (IFNGR2, HCG22, IL12B, BTN3A2, and TRIM40) showed protective effects against PsO progression. Robust colocalization (PPH₄ > 0.9) identified IFNLR1, IFNGR2, APOF, and TDRKH as top candidates. Single-cell RNA sequencing analysis revealed that IFNLR1, IFNGR2, LTA, TDRKH, and DDR1 were specifically expressed in T cells of psoriatic biopsy specimens compared to healthy controls. Molecular docking indicated the druggability of IFNLR1 and IFNGR2. Conclusions: We identified several potential therapeutic targets for PsO, with IFNLR1, IFNGR2, APOF, and TDRKH emerging as promising candidates, particularly IFNLR1 and IFNGR2, which are associated with the IFN family. These findings may provide new perspectives on PsO therapy and pathogenesis. Full article

Hepatitis B and C (HBV and HCV) infections persist as significant public health concerns. Specific occupational groups, such as waste collectors, continue to face elevated risk due to exposure to contaminated materials. Research studies have underscored heightened infection rates, notably from needle prick injuries. The present study aspires to re-evaluate the prevalence of HBV and HCV among waste collectors and to scrutinize associated risk factors, thereby contributing to the development of effective public health and occupational safety strategies. The study analyzed data from 116 Italian waste collectors who were undergoing regular occupational visits, examining demographics, health conditions, HBV immunization, and annual blood tests for the HBsAg, HBsAb, and HCVAb. The HBsAb was detected in 66 individuals (56.9%), while the HCVAb was found in 4 (3.4%). Logistic regression showed HBV immunization and longer job experience to be significant factors associated with HBsAb presence. Waste collection may increase HBV infection risk due to occupational exposure, unlike HCV, which requires blood-to-blood contact. Preventive strategies, including education, protective equipment, and HBV vaccination, are essential. Ensuring vaccination coverage among waste collectors could reduce infection risk. Further research should assess the occupational risks and the effectiveness of preventive measures. Full article

Background/Objectives: The complement system (particularly C5b-9) is an instrumental part of the induction and progression of atherosclerosis. The fluid phase C5b-9, also known as soluble C5b-9 (sC5b-9), is a reliable indicator of terminal complement pathway activation. Response Gene to Complement (RGC)-32 is a C5b-9 effector involved in cell cycle regulation and differentiation, immunity, tumorigenesis, obesity, and vascular lesion formation. RGC-32 regulates the expression of Sirtuin1 (SIRT1), known to delay vascular aging. The aim of this study was to assess the levels of sC5b-9, RGC-32, and SIRT1 in patients with atherosclerotic chronic and acute ischemic coronary syndromes. Methods: We determined the levels of sC5b-9, serum RGC-32, and SIRT1 by enzyme-linked immunosorbent assays (ELISAs) in 41 patients with chronic atherosclerotic coronary syndromes, 36 patients with acute ischemic coronary syndromes, and 21 asymptomatic controls with no history of ischemic heart disease. Results: sC5b-9 was significantly higher in patients with acute coronary syndrome as compared to the control group (p = 0.020, AUC = 0.702). In chronic coronary ischemia patients, serum RGC-32 was correlated with the extension of coronagraphically visualized atherosclerotic lesions (r = 0.352, p = 0.035) as well as with sC5b-9 levels (r = 0.350, p = 0.025). RGC-32 concentration was significantly lower in patients with acute coronary syndrome than in the control group (p = 0.020). We also observed significantly lower serum SIRT1 concentrations in patients with chronic ischemic heart disease than in the control group (p = 0.025). Conclusions: sC5b-9 may function as a possible biomarker for myocardial tissue damage in acute coronary syndrome. In acute coronary syndrome settings, low levels of RGC-32 may indicate a protective, antifibrotic function of RGC-32 in the ischemia-damaged myocardium; however, in stable chronic disease, RGC-32 serum values appear to correlate with the extent of atherosclerotic lesions, suggesting a pro-atherogenic role for RGC-32. Chronic myocardial ischemia decreases SIRT1 protein levels in serum, which underscores the use of SIRT1-modulating drugs in these patients. Full article

A diverse bacterial community colonizes the respiratory system, including commensals such as Staphylococcus epidermidis (S. epidermidis) and Streptococcus salivarius (S. salivarius), as well as facultative pathogens like Staphylococcus aureus (S. aureus). This study aimed to establish a colonized cell culture model to investigate the impact of these bacteria on influenza A virus (IAV) infection. Respiratory epithelial cells were exposed to S. epidermidis, S. salivarius, or S. aureus, using either live or heat-inactivated bacteria, followed by IAV infection. Cell integrity was assessed microscopically, cytotoxicity was measured via LDH assay, and inflammatory responses were analyzed through cytokine expression. Additionally, macrophage function was examined in response to bacterial colonization and IAV infection. While commensals maintained epithelial integrity for 48 h, S. aureus induced severe cell damage and death. The most pronounced epithelial destruction was caused by coinfection with S. aureus and IAV. Notably, commensals did not confer protection against IAV but instead enhanced epithelial inflammation. These effects were dependent on live bacteria, as inactivated bacteria had no impact. However, prior exposure to S. epidermidis and S. salivarius improved macrophage-mediated immune responses against IAV. These findings suggest that while individual commensals do not directly protect epithelial cells, they may contribute to immune training and enhance lung defense mechanisms. Full article

Background and Objectives: Acute ulcerative colitis is characterized by excessive mucosal inflammation and epithelial disruption, often driven by dysregulated cytokine and immune signaling. Indoximod (1-methyl-DL-tryptophan), although not a direct enzymatic inhibitor, modulates the indoleamine 2,3-dioxygenase (IDO) pathway and has been reported to exert immunoregulatory effects in various models of inflammation. This study aimed to evaluate the protective effects of Indoximod in an acetic acid-induced colitis model in rats, focusing on histopathological changes and inflammatory mediators. Materials and Methods: Thirty male Wistar albino rats were randomly assigned to three groups (n = 10 per group): Group 1 (Control) received 0.9% saline oral gavage; Group 2 (Colitis) received intrarectal 4% acetic acid to induce colitis and were then treated with saline; Group 3 (Colitis + Indoximod) received 4% acetic acid followed by oral gavage administration of Indoximod (30 mg/kg) for 15 consecutive days. Histopathological evaluation of colonic tissues was performed using hematoxylin and eosin (H&E) staining. Colonic expression of Toll-like receptor 4 (TLR4) and plasma levels of tumor necrosis factor-alpha (TNF-α), pentraxin-3 (PTX-3), and platelet-activating factor (PAF) were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Acetic acid-induced colitis significantly increased mucosal damage, TLR4 expression, and circulating levels of TNF-α, PTX-3, and PAF compared with controls (p < 0.001). Indoximod treatment markedly reduced histological injury and significantly suppressed TLR4 and TNF-α levels (p < 0.01), along with partial reductions in PTX-3 (p < 0.05). However, PAF levels remained elevated despite treatment, indicating limited efficacy in PAF-associated pathways. Conclusions: Indoximod exhibited anti-inflammatory effects in this acute colitis model, likely by downregulating key proinflammatory mediators. Full article

The introduction of pneumococcal conjugate vaccination (PCV) into the Argentinian Childhood National Immunization Program in 2012 marked a significant milestone in public health. Our study aims to assess the impact of this intervention on pneumococcal meningitis cases, serotype distribution, and antimicrobial resistance among pediatric populations from 2013 to 2023. Specifically, we compared the early post-PCV period (2013–2014) to the late post-PCV period (2022–2023). A total of 333 pneumococcal isolates were analyzed between 2013 and 2023. Gold standard pneumococcal serotyping was performed to identify the serotypes associated with infection in children < 6 years in Argentina, and the agar dilution method was carried out to determine their profiles to antimicrobial agents. Our findings underscore the importance of PCV implementation, revealing notable shifts in pneumococcal epidemiology over the study period. The proportions of serotypes 1 (6.7% to 0.0%), 5 (5.6% to 0.0%), and 14 (7.8% to 1.8%) decreased, whereas the proportions of serotypes 10A (3.3% to 10.7%), 15B/C (2.2% to 10.7%), and 24B (0.0% to 8.9%) increased. The top five rated serotypes in the 2022–2023 period were serogroup 24 (21.4%), 10A (10.7%), 15B/C (10.7%), 23B (7.1%), and 12F (5.4%). Regarding antimicrobial resistance, we found that a total of 115/311 isolates (37%) were not suceptible to penicillin, and 2.9% were not suceptible to cefotaxime. Twenty-five percent of the isolates were microbial drug resistant, with resistance to penicillin, erythromycin, tetracycline/doxicycline, and/or cotrimoxazol. Among the PCV13 serotypes, 19A remained the most commonly associated with MDR. The non-PCV13 serotypes, particularly 24F, 24A, and 24B, were prevalent among MDR isolates. The observed trends demonstrate the need for the continued expansion of pneumococcal vaccination policies, including consideration for vaccines offering enhanced indirect protection, thereby extending benefits beyond the pediatric population to encompass adults as well. Such strategies are pivotal in reducing the burden of pneumococcal disease and safeguarding public health. Full article

Foot-and-mouth disease virus (FMDV) continues to pose a significant threat to livestock health and the global agricultural economy, particularly in endemic regions of Asia, Africa, and the Middle East. Current vaccines based on chemically inactivated FMDV present several challenges, including biosafety risks, high production costs, and limited effectiveness against emerging viral variants. To overcome these limitations, we developed virus-like particle (VLP) vaccines targeting FMDV serotypes O, A, and Asia1 using a recombinant Escherichia coli expression system. The resulting VLPs self-assembled into 25–30 nm particles with native-like morphology and antigenic properties, as confirmed by transmission electron microscopy, SDS-PAGE, and Western blot analysis. Immunogenicity was evaluated in mice and pigs using ELISA and virus neutralization tests (VNT), and protective efficacy was assessed through viral challenge studies. All VLPs induced strong serotype-specific antibody responses, with ELISA PI values exceeding 50% and significantly increased VNT titers after booster immunization. In mice, PD₅₀ values were 73.5 (A-type), 32.0 (O-type), and 55.7 (Asia1-type); in pigs, PD₅₀ values reached 10.6 (O-type) and 22.6 (Asia1-type). Notably, the vaccines induced robust immune responses even at lower antigen doses, suggesting the feasibility of dose-sparing formulations. These findings demonstrate that FMDV VLPs produced in E. coli are highly immunogenic and capable of eliciting protective immunity, highlighting their promise as safe, scalable, and cost-effective alternatives to conventional inactivated FMD vaccines. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract with rising incidence and an unclear etiology. Innate lymphoid cells (ILCs) have recently emerged as key regulators of mucosal immunity and tissue homeostasis and are increasingly implicated in IBD. Unlike adaptive lymphocytes, ILCs do not require antigen recognition and clonal expansion to respond rapidly to environmental cues and shape immune responses. In a healthy gut, ILCs maintain intestinal homeostasis by guarding the epithelial barrier, protecting against pathogens, and mounting proper responses to external insults. However, their altered differentiation, proliferation, recruitment, activation, and interaction with other host cells, microbiota, and environmental stimuli may contribute to IBD. In this review, we discuss recent advances in understanding murine and human ILCs in the context of intestinal inflammation and IBD. A deeper understanding of ILC-mediated immune mechanisms may offer novel therapeutic strategies for restoring intestinal homeostasis and improving personalized management of IBD. Full article

The high variability of human leukocyte antigen (HLA) genes results in each molecule having distinct antigenic peptide binding capacities, potentially influencing the immune response to SARS-CoV-2. This study aimed to investigate associations between HLA class I (A, B) and class II (DRB1) polymorphisms and COVID-19 severity in a South Brazilian population, and to evaluate the binding affinity of alleles to viral peptides. A cross-sectional study included 503 unvaccinated patients with RT-qPCR-confirmed COVID-19: 145 non-severe, 129 severe, and 229 critical. HLA typing was performed using PCR-SSO and Luminex™ technology. The DRB1*11 allelic group was significantly associated with protection against severe and critical cases, while DRB1*15 was associated with increased risk; both remained significant after Bonferroni correction. Other allelic groups were associated with disease outcomes but lost significance after correction: B*49 and B*08 (risk); and B*37, B*50, and A*03 (protection). In silico analysis revealed that the DRB1*15 allele group showed a higher proportion of strong binders, mostly from non-structural proteins, while DRB1*11:01 binders, though fewer in number, were concentrated in the M protein. These results suggest functional differences in antigen presentation and reinforce the relevance of class II HLA, particularly DRB1, in modulating COVID-19 severity. Full article

Leishmaniasis are infectious diseases caused by several parasitic species of Leishmania, mainly transmitted by the bite of infected phlebotomine sandflies. Humans, dogs, rodents, and other domestic and wild animals can act as reservoir hosts for the different Leishmania species. It is a neglected tropical disease that is endemic in Asia, the Middle East, North and East Africa, the Mediterranean region, and South and Central America. Clinical manifestations and disease severity depend on the species of the infecting parasites and the immunity status of the host. Leishmania represses the protective host immune response by manipulating the macrophage function, subverting cytokine expression to favor its survival and dissemination. A balance between pro-inflammatory and regulatory cells is necessary to bring a positive outcome. Accurate diagnosis and effective treatment represent the cornerstone in the control of this disease, although these are difficult in an environment of precariousness and poverty. Some recent studies highlighted the progressing work on diagnosis and treatments, such as the development of new benzimidazole-triazole derivatives for blocking the parasite growth, feline leishmaniasis with a comparison of immune responses in cats and dogs, and a transglutaminase that has been purified from L. infantum. The results of these studies could open new avenues in combating leishmaniasis. Full article