Search Results (2,450)

mRNA-LNP-based COVID-19 vaccines, namely Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, were successfully deployed to help control the SARS-CoV-2 pandemic, and their updated formulations continue to be recommended, albeit only for high-risk populations. One widely discussed aspect of these vaccines is their uniquely broad spectrum and increased incidence of adverse events (AEs), collectively referred to as post-vaccination syndrome (PVS). Although the reported PVS rate is low, the high number of administered doses among healthy individuals has resulted in a substantial number of reported vaccine-related injuries. A prominent manifestation of PVS is multisystem inflammation, hypothesized to result from the systemic transfection of organ cells with genetic instructions for a toxin, the spike protein, delivered with lipid nanoparticles (LNPs). In this narrative review, we focus on endothelial cells in the microcirculatory networks of various organs as primary sites of transfection with mRNA-LNP and consequent PVS. We outline the anatomical variations in the microcirculation contributing to the individual variability of symptoms and examine the molecular and cellular responses to vaccine nanoparticle exposure at the endothelial cell level with a focus on the pathways of a sustained cascade of toxic and autoimmune processes. A deeper understanding of the mechanisms underlying mRNA-LNP-induced AEs and PVS at the organ and cellular levels is critical for improving the safety of future vaccines and other therapeutic applications of this groundbreaking technology. Full article

Respiratory syncytial virus (RSV) remains a leading cause of acute lower respiratory tract infections globally, particularly affecting infants, older adults, and immunocompromised individuals. While recent advances in prophylaxis, such as long-acting monoclonal antibodies and maternal immunization, offer promise for prevention, therapeutic options for active infection remain limited. Severe RSV disease is often driven not solely by viral replication but by dysregulated host immune responses, including excessive cytokine production, T helper type 2 (Th2) and T helper type 17 (Th17) cell polarization, and impaired interferon signaling. RSV has evolved sophisticated immune evasion strategies, such as inhibition of dendritic cell maturation, degradation of signal transducer and activator of transcription 2 (STAT2) via nonstructural proteins 1 and 2 (NS1/NS2), and interference with pattern recognition receptor signaling, particularly Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors. These mechanisms result in attenuated innate immune responses and defective adaptive immunity, contributing to viral persistence, immunopathology, and recurrent infections. Moreover, age-dependent vulnerabilities, such as immune immaturity in infants and immunosenescence in older adults, exacerbate disease severity. Excessive immune activation leads to bronchiolitis, airway remodeling, and long-term sequelae including wheezing and asthma. Emerging immunomodulatory therapies aim to restore immune balance, targeting cytokines (e.g., interleukin-6 [IL-6], interleukin-1 beta [IL-1β]), the Janus kinase–signal transducer and activator of the transcription (JAK-STAT) pathway, or inflammasome activity. Host-directed therapies and direct-acting antivirals are also under investigation. A better understanding of RSV–host immune interactions is critical for optimizing therapeutic strategies and designing effective vaccines. This review synthesizes current knowledge on RSV immunopathogenesis and highlights immunomodulation as a promising frontier for therapeutic intervention. Full article

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory dermatosis of the pilosebaceous unit characterized by nodules, abscesses, and dermal tunnels. Recent transcriptomic studies have implicated dysregulation of innate and adaptive immune responses, epidermal barrier dysfunction, and systemic metabolic alterations. This review synthesizes findings from 16 studies investigating the HS transcriptome using bulk and single-cell RNA sequencing. Differential gene expression analyses revealed extensive upregulation of inflammatory cytokines and chemokines, particularly in lesional and perilesional skin. These changes were also mirrored in non-lesional skin, suggesting diffuse immune dysregulation beyond visibly affected areas. Downregulated pathways include those involved in lipid metabolism, muscle contraction, and neuronal signaling, potentially linking HS to obesity, metabolic syndrome, and neuropsychiatric comorbidities. Single-cell transcriptomics confirmed the enrichment of keratinocytes and immune cells (B cells, plasma cells, M1 macrophages, and T cells) with proinflammatory profiles in HS lesions. Keratinocyte dysfunction further implicated a compromised epidermal barrier in disease pathogenesis. While transcriptomic studies have advanced mechanistic understanding and highlighted therapeutic targets—such as the IL-1β–TH17 axis and B cell signaling pathways—methodological heterogeneity limits cross-study comparisons. Integration of multi-omics data and standardized phenotyping will be essential to identify robust biomarkers, stratify HS subtypes, and guide personalized therapeutic approaches. Full article

Two key players in the immune system, dendritic cells (DCs) and innate lymphoid cells (ILCs), interact in a crucial way to fight infectious diseases. DCs play a key role in recognizing pathogens, and ILCs respond to cytokines released by DCs. This response triggers the production of specific effector cytokines that help control pathogens and maintain the body’s barrier integrity. DCs have various receptors, including Toll-like receptors (TLRs), that detect microbial components and trigger immune responses. Likewise, ILCs act as essential initial responders in the immune system in viral, bacterial, and parasitic infections. Successfully managing diseases caused by pathogens mainly depends on the combined actions of DCs and ILCs, which work to suppress and eliminate pathogens. DCs also play a crucial role in activating innate and adaptive immune cell subsets, including ILCs. Furthermore, the use of DCs in developing vaccines and immunotherapy for cancers, along with the dedication of many researchers to improve immune responses through DCs, has increased interest in the potential of DC therapies for treating and preventing infectious diseases. This review examines approaches that may enhance DC vaccines and boost anti-infection immune responses by fostering better interactions of DCs with ILCs. Full article

This paper proposes a novel defense mechanism inspired by the bioimmune response to effectively eliminate botnets that repeatedly infect IoT networks and describes the development of an Immune-Based Botnet Defense System (iBDS), incorporating this mechanism. Focusing on the roles of antibodies and phagocytes in the immune response, the iBDS implements a multi-layered defense using two types of worms: antibody worms and phagocyte worms. When a malicious botnet infects a network, the resident phagocyte worms immediately infect and eliminate the bots and prevent the infection from spreading in its early stages. This provides an immediate response in a similar way to innate immunity. On the other hand, if a malicious botnet infects the network and the phagocyte worms are unable to infect the bots, the antibody worms, instead, infect the bots and change their vulnerabilities to help the phagocyte worms infect and eliminate them. This provides an adaptive response in a similar way to acquired immunity. In addition, when the same botnet is repeatedly infected, more antibody worms are used to produce a stronger response, similar to immune memory. The introduction of multi-layered defense and immune memory is an important novelty of this paper that is not found in traditional botnet defense system research. The experimental results from simulations and prototype implementations show that iBDS can effectively eliminate botnets that repeatedly infect IoT networks. Full article

Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity. Furthermore, IFNAR blockade rescues ILC3 functionality, which is critical for IL-17/IL-22-mediated antimicrobial defense and mucosal barrier maintenance. Our study delineates IFN-I-driven immunosuppression across innate lymphocyte compartments and proposes the targeted modulation of this pathway to enhance antiviral and mucosal immunity in HIV-1 management. Full article

Sex-based immunological differences significantly influence the outcome of vaccination, yet the molecular mediators underpinning these differences remain largely elusive. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have emerged as critical modulators of innate and adaptive immune responses. In this study, we investigated the expression profile of selected circulating miRNAs as potential biomarkers of sex-specific humoral responses to the mRNA COVID-19 vaccine in a cohort of health care workers. Plasma samples were collected longitudinally at a defined time point (average 71 days) post-vaccination and analyzed using RT-qPCR to quantify a panel of immune-relevant miRNAs. Anti-spike (anti-S) IgG titers were measured by chemiluminescent immunoassays. Our results revealed sex-dependent differences in miRNA expression dynamics, with miR-221-3p and miR-148a-3p significantly overexpressed in vaccinated female HCWs and miR-155-5p overexpressed in vaccinated males. MiR-148a-3p showed a significant association with anti-S/RBD (RBD: receptor binding domain) IgG levels in a sex-specific manner. Bioinformatic analysis for miRNA targets indicated distinct regulatory networks and pathways involved in innate and adaptive immune responses, potentially underlying the differential immune activation observed between males and females. These findings support the utility of circulating miRNAs as minimally invasive biomarkers for monitoring and predicting sex-specific vaccine-induced immune responses and provide mechanistic insights that may inform tailored vaccination strategies. Full article

Traditional anti-inflammatory medications—such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs—are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we provide an overview of the selective infiltration of AuNPs into immune cells and summarize their interactions with and impact on these cells. Additionally, we provide a comprehensive mechanistic summary of how AuNPs exert their anti-inflammatory effects. Full article

Conventional immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, has revolutionized cancer therapy over the past decade. Yet, the efficacy of these therapies is limited by tumor resistance, antigen escape mechanisms, poor persistence, and T-cell exhaustion, particularly in the treatment of solid tumors. The emergence of unconventional immunotherapies offers novel opportunities by leveraging diverse immune cell subsets and synthetic biologics. This review explores various immunotherapy platforms, including gamma delta T cells, invariant natural killer T cells, mucosal-associated invariant T cells, engineered regulatory T cells, and universal CAR platforms. Additionally, it expands on biologics, including bispecific and multispecific antibodies, cytokine fusions, agonists, and oncolytic viruses, showcasing their potential for modular engineering and off-the-shelf applicability. Distinct features of unconventional platforms include independence from the major histocompatibility complex (MHC), tissue-homing capabilities, stress ligand sensing, and the ability to bridge adaptive and innate immunity. Their compatibility with engineering approaches highlights their potential as scalable, efficient, and cost-effective therapies. To overcome translational challenges such as functional heterogeneity, immune exhaustion, tumor microenvironment-mediated suppression, and limited persistence, novel strategies will be discussed, including metabolic and epigenetic reprogramming, immune cloaking, gene editing, and the utilization of artificial intelligence for patient stratification. Ultimately, unconventional immunotherapies extend the therapeutic horizon of cancer immunotherapy by breaking barriers in solid tumor treatment and increasing accessibility. Continued investments in research for mechanistic insights and scalable manufacturing are key to unlocking their full clinical potential. Full article

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells, resulting in lifelong insulin dependence. While genetic susceptibility—particularly human leukocyte antigen (HLA) class II alleles—is a major risk factor, accumulating evidence implicates viral infections as potential environmental triggers in disease onset and progression. This narrative review synthesizes current findings on the role of viral pathogens in T1DM pathogenesis. Enteroviruses, especially Coxsackie B strains, are the most extensively studied and show strong epidemiological and mechanistic associations with beta-cell autoimmunity. Large prospective studies—including Diabetes Virus Detection (DiViD), The environmental determinans of diabetes in the young (TEDDY), Miljøfaktorer i utvikling av type 1 diabetes (MIDIA), and Diabetes Autoimmunity Study in the Young (DAISY)—consistently demonstrate correlations between enteroviral presence and the initiation or acceleration of islet autoimmunity. Other viruses—such as mumps, rubella, rotavirus, influenza A (H1N1), and SARS-CoV-2—have been investigated for their potential involvement through direct cytotoxic effects, immune activation, or molecular mimicry. Interestingly, certain viruses like varicella-zoster virus (VZV) and cytomegalovirus (CMV) may exert modulatory or even protective influences on disease progression. Proposed mechanisms include direct beta-cell infection, molecular mimicry, bystander immune activation, and dysregulation of innate and adaptive immunity. Although definitive causality remains unconfirmed, the complex interplay between genetic predisposition, immune responses, and viral exposure underscores the need for further mechanistic research. Elucidating these pathways may inform future strategies for targeted prevention, early detection, and vaccine or antiviral development in at-risk populations. Full article

Toxoplasma gondii is an intracellular protozoan found worldwide that is capable of infecting nearly all warm-blooded animals, including humans. Its parasitic success lies in its capacity to create chronic infections while avoiding immune detection, altering host immune responses, and disrupting programmed cell death pathways. This review examines the complex relationship between T. gondii and host immunity, focusing on how the parasite influences innate and adaptive immune responses to survive in immune-privileged tissues. We present recent findings on the immune modulation specific to various parasite strains, the immunopathology caused by imbalanced inflammation, and how the parasite undermines host cell death mechanisms such as apoptosis, necroptosis, and pyroptosis. These immune evasion tactics enable prolonged intracellular survival and pose significant challenges for treatment and vaccine development. We also review advancements in therapeutic strategies, including host-directed approaches, nanoparticle drug delivery, and CRISPR-based technologies, along with progress in vaccine development from subunit and DNA vaccines to live-attenuated candidates. This review emphasizes the importance of T. gondii as a model for chronic infections and points out potential avenues for developing innovative therapies and vaccines aimed at toxoplasmosis and similar intracellular pathogens. Full article

This study investigated the immunonutritional potential of high-molecular-weight (Mw~85 kDa), non-degraded chitosan (NCS) and gamma-radiation-degraded, low-molecular-weight chitosan (RCS) incorporated into aquafeeds for Nile tilapia (Oreochromis niloticus). RCS was produced by γ-irradiation (10 kGy) in the presence of 0.25% (w/v) H₂O₂, yielding low-viscosity, colloidally stable nanoparticles with Mw ranging from 10 to 13 kDa. Five diets were formulated: a control, NCS at 0.50%, and RCS at 0.025%, 0.050%, and 0.075%. No adverse effects on growth were observed, confirming safety. Immune gene expression (e.g., ifng1, nfκb, tnf), antioxidant markers (e.g., reduced MDA, increased GSH and GR), and nonspecific humoral responses (lysozyme, IgM, and bactericidal activity) were significantly enhanced in the NCS-0.50, RCS-0.050, and RCS-0.075 groups. Notably, these benefits were achieved with RCS at 10-fold lower concentrations than NCS. Following challenge with Edwardsiella tarda, fish fed RCS-0.050 and RCS-0.075 diets exhibited the highest survival rates and relative percent survival, highlighting robust activation of innate and adaptive immunity alongside redox defense. These results support the use of low-Mw RCS as a biologically potent, cost-effective alternative to traditional high-Mw chitosan in functional aquafeeds. RCS-0.050 and RCS-0.075 show strong potential as immunonutritional agents to enhance fish health and disease resistance in aquaculture. Full article

Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Helicobacter pylori infection represents one of the most prevalent and persistent bacterial infections worldwide, closely linked to a spectrum of gastroduodenal diseases, including chronic gastritis, peptic ulceration, and gastric cancer. Recent advances have shed light on the critical role of endogenous lectins, particularly galectins, in modulating host–pathogen interactions within the gastric mucosa. Galectins are β-galactoside-binding proteins with highly conserved structures but diverse biological functions, ranging from regulation of innate and adaptive immunity to modulation of cell signaling, apoptosis, and epithelial integrity. This review provides a comprehensive synthesis of current knowledge on the involvement of key galectin family members—especially Galectin-1, -2, -3, -8, and -9—in the context of H. pylori infection. Their dual roles in enhancing mucosal defense and facilitating bacterial persistence are examined along with their contributions to immune evasion, inflammation, and gastric carcinogenesis. Understanding the interplay between galectins and H. pylori enhances our knowledge of mucosal immunity. This interaction may also reveal potential biomarkers for disease progression and identify novel therapeutic targets. Modulating galectin-mediated pathways could improve outcomes in H. pylori-associated diseases. Full article