Search Results (1,908)

Phage therapy (PT) is a promising alternative for antibiotic-resistant infections, but its immunomodulatory effects in clinical settings remain poorly understood. This exploratory observational study aimed to characterize pro- and anti-inflammatory gene response patterns in ten patients undergoing personalized PT at the Phage Therapy Unit in Wrocław. Peripheral blood mononuclear cells (PBMCs) and granulocytes were analyzed to assess changes in the expression of 22 selected immune-related genes associated with innate and adaptive immune signaling pathways. While no uniform pattern of immune gene expression was observed across the cohort, individual cases exhibited significant up- or downregulation of specific genes. Interestingly, we identified biological age as a potential determinant of the host response. Specifically, older patients showed higher activation of the innate sensing machinery in PBMCs, characterized by a higher TLR4 fold change which may reflect the “inflammaging” phenomenon. These findings suggest that chronic exposure to bacterial viruses (bacteriophages), unlike many viral infections, does not trigger a predictable, significant systemic immune activation and that immune responses to PT are highly individualized by host- and phage-related biological factors. By documenting this spectrum of real-world responses, our work provides baseline data and hypotheses to guide the rational design of future preclinical and clinical investigations. Full article

Background: Pentraxin 3 (PTX3) is a key biomarker of innate immunity and inflammation, associated with muscle mass, metabolic syndrome, and obesity-related indicators. However, its role in training adaptations remains unclear, with studies reporting inconsistent PTX3 responses to acute and chronic exercise. This study aimed to compare the effects of aerobic exercise, resistance training, high-intensity interval training (HIIT), and acute exercise on PTX3 levels. Methods: A systematic search using Boolean logic was conducted in Web of Science, PubMed, and Google Scholar to identify randomized controlled trials examining the effects of exercise training and acute exercise on PTX3 levels. Results: Out of 3434 records published from 1992 to July 2025, 19 studies met the eligibility criteria. Meta-analysis revealed that aerobic training significantly increased PTX3 levels (SMD = 0.71; 95% CI, 0.173 to 1.252; p = 0.01; I² = 83.14%), whereas resistance training significantly reduced them (SMD = −0.69; 95% CI, −1.025 to −0.370; p = 0.0001; I² = 17.52%). HIIT did not elicit a significant change (SMD = 0.086; 95% CI, −0.364 to 0.535; p = 0.70; I² = 0.00%). Notably, exercise training significantly elevated PTX3 in individuals over 50 years old (SMD = 1.124; 95% CI, 0.231 to 2.017; p = 0.014; I² = 87.97%) but not in younger participants (SMD = −0.156; 95% CI, −0.640 to 0.327; p = 0.526; I² = 78.80%). Conclusion: Aerobic and resistance exercise exert opposing effects on PTX3, suggesting distinct mechanisms through which different training modalities modulate inflammatory pathways relevant to muscle metabolism and repair. Acute exercise may also transiently elevate PTX3 to manage exercise-induced inflammation. Full article

Human leukocyte antigen (HLA)-E, a non-classical class I molecule with limited polymorphism, bridges innate and adaptive immunity. Traditionally, the role of HLA-E had been associated with regulating natural killer (NK) cell activity via CD94/NKG2 receptors, by presenting self-peptides derived from the leader sequence of HLA-I. Recent findings reveal its ability to present pathogen-derived peptides to CD8⁺ T cells, eliciting unconventional cytotoxic responses. This review examines the expanding role of HLA-E-restricted T cells in viral and bacterial infections and their capacity to recognize diverse microbial peptides and enhance immune response when classical HLA pathways are impaired. We also highlight key advances in immunotherapy and vaccine development, including CMV-vectored platforms, donor-unrestricted TCR-based strategies, and peptide prediction algorithms. The minimal polymorphism of HLA-E, its resistance to viral immune evasion, and its ability to present conserved pathogen peptides position it as a promising target for universal vaccines and next-generation immunotherapies. Understanding these unconventional roles may pave the way for broadly applicable immunotherapies and vaccines against infectious diseases. Full article

Trichomoniasis is the most common non-viral sexually transmitted infection in humans, with over 200 million people affected each year. This disease is associated with pre-term birth, low birth weight, and premature membrane rupture. Its causal pathogen, Trichomonas vaginalis (TV), is a prevalent sexually transmitted protozoan parasite that infects the urogenital tract through cytoadherence. TV infection alters TV gene expression and induces host immune responses, while TV-secreted exosomes carry RNA and protein cargoes that mediate extracellular signaling. This review summarizes recent discoveries of molecules that interact with host receptors involved in cytoadherence. We also discuss human innate and adaptive immune responses to TV infection via a variety of inflammatory mediators. Recent research on concurrent or endosymbiont relationships of TV with other urogenital microbes and cancers, is also examined. These studies not only highlight the necessity of understanding host–microbe interactions in TV pathogenesis but also provide a crucial insight into potential therapeutic targets of nitroimidazole-resistant TV strains. Full article

While the distinct roles of lymphocyte populations are well characterized in adaptive immunity, the phenotypic and functional diversity of innate immune cells is less explored. In recent years, subsets of monocytes have gained attention, as prominent shifts in population frequencies have been observed in disease states such as cancer. This narrative review summarizes current knowledge of the distribution and functional differences among the three major monocyte subsets (classical, intermediate, non-classical) in tumor settings. It includes rare populations, such as neutrophil-like, CD56+, and Tie2-expressing monocytes. Scientific evidence indicates that the phenotypical and functional heterogeneity of monocyte subsets determines their roles in either preventing cancer development or supporting the progression of disease through a remarkable diversity of mechanisms. Of note, alterations in the distribution of monocyte subsets and their functional reprogramming have been identified as drivers of cancer progression. While changes in monocyte frequencies have limited diagnostic biomarker potential for cancer detection, they may reflect the progression of disease and response to therapy. Based on subset-specific properties, distinct monocyte populations are increasingly recognized as promising targets of cancer immunotherapy. Yet novel strategies targeting monocyte populations must consider the risk of treatment reversal given the high plasticity of these cells. Full article

Bats, as the world’s second-largest mammalian order, have garnered significant attention for their ability to harbor numerous viruses without exhibiting disease symptoms. Nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) are crucial components of the immune system. This study conducted an evolutionary analysis of the NLR gene family across 26 bat species to investigate the molecular mechanisms underlying their role in viral resistance under high viral load pressure. We identified gene duplication events in multiple genes. The NLR gene family exhibited high conservation throughout evolution, which may contribute to the occurrence of gene duplication. This conserved genomic structure also ensures functional stability, safeguarding bats’ antiviral resistance. Most NLR genes primarily function within the type I interferon (IFN) signaling pathway and the NF-κB signaling pathway. The NLR gene family enhances the innate immune capacity of bats through the adaptive evolution of some genes, combining enhanced gene functionality with the maintenance of gene conservation at a low evolutionary rate. Moreover, bats employ diverse innate immune strategies, where multiple immune pathways collectively establish the innate immune barrier. The molecular evolution of this gene family provides new insights into the molecular mechanisms and functional pathways involved in the innate immune response of bats. Full article

The relationship between asthma, infections, and immunodeficiencies is complex and affects disease progression. Immune deficiencies can occur independently or because of the inflammatory processes associated with asthma. Early viral infections like respiratory sinticial virus and rhinovirus trigger asthma attacks, while bacteria such as Haemophilus influenzae, Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydia pneumoniae worsen airway inflammation. People with asthma often have defects in innate (mucociliary clearance, interferons, defensins, NK cell, and eosinophils) and adaptive immunity such as immunoglobulin (Ig) deficiencies, making them more vulnerable to lung infections. Combined and selective deficiencies of IgA, IgG, IgM, and IgE are linked to higher asthma rates and reduced effectiveness of treatments, but immunoglobulin therapy can help control symptoms. Biologic therapies also decrease asthma exacerbations during periods of high viral activity by boosting immune responses and airway defenses. However, the link between asthma and higher infection risk is not well studied or understood, so guidelines do not recommend routinely checking for immunodeficiencies in cases of poor treatment response. Further investigation is required to elucidate these relationships and enhance management approaches. Full article

PANoptosis is an integrated form of regulated cell death that combines pyroptosis, apoptosis, and necroptosis through a coordinated molecular platform known as the PANoptosome. Autophagy, in parallel, maintains immune homeostasis by controlling cellular stress responses. Although both pathways are essential for innate and adaptive immunity, their functional interplay has only recently been explored. This review summarizes current knowledge on the bidirectional relationship between PANoptosis and autophagy, with emphasis on how autophagy can restrain PANoptotic signaling or, under certain conditions, promote inflammatory cell death. We discuss cell-type-specific aspects of this crosstalk in macrophages, dendritic cells, monocytes, neutrophils, T cells, and B cells, focusing on key PANoptosis mediators and autophagy-related proteins. We then examine how dysregulated autophagy and exaggerated PANoptotic signaling contribute to chronic inflammation and tissue damage in immune-mediated inflammatory disease, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, psoriasis, and inflammatory bowel disease. Finally, we outline shared molecular principles that position the autophagy–PANoptosis axis as a fundamental immunoregulatory mechanism and a promising source of therapeutic targets in chronic inflammatory and autoimmune disorders. Full article

Research Subject: Primary and secondary immunodeficiencies represent a growing clinical and public health challenge due to increased susceptibility to infections, impaired immune regulation, chronic inflammation, and disturbances in redox homeostasis. The pathophysiology of these disorders involves dysfunction of innate and adaptive immunity, altered cytokine production, oxidative stress, and reduced activity of antioxidant defense mechanisms. In recent years, attention has increasingly focused on the role of oxidative imbalance and chronic inflammation in weakening immune function. Ozone therapy, when used at controlled low doses, induces a hormetic response that triggers adaptive antioxidant pathways, modulates cytokine profiles, and enhances the activity of immune cells. Due to these properties, ozone has emerged as a potential adjunctive therapy aimed at restoring immune homeostasis and improving clinical outcomes in patients with immune disorders. Aim of Study: The aim of this review is to discuss the role of oxidative stress and immune dysregulation in the pathogenesis of immunodeficiencies and to provide an updated overview of current evidence regarding the therapeutic potential of ozone therapy. This article summarizes molecular mechanisms, biochemical effects, and clinical findings related to ozone-based interventions, with particular emphasis on cytokine modulation, redox balance, macrophage function, regulatory T cells (Treg), and NK cell activity. Materials and Methods: This review is based on scientific data retrieved from PubMed, Scopus, and Google Scholar. Included sources comprise randomized clinical trials, observational studies, meta-analyses, mechanistic studies, and review articles published between 1996 and 2025. Keywords used during the literature search included: “ozone therapy”, “immunomodulation”, “oxidative stress”, “inborn errors of immunity”, “secondary immunodeficiency”, “Treg cells”, “redox homeostasis”. Results: Analysis of current studies shows that controlled low-dose ozone (typically 10–40 µg/mL) activates the Nrf2/ARE antioxidant pathway, increases enzymatic defense (SOD, catalase, GPx), and reduces levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. Clinical trials report improved lymphocyte profiles, enhanced macrophage phagocytic function, increased Treg activity, and reinforced NK cell responses. Patients receiving ozone therapy demonstrate reductions in inflammatory markers (CRP, IL-6, D-dimer), improved redox balance, decreased infection frequency, and better overall immune performance. The therapy is generally well tolerated when administered within established safety guidelines. Conclusions: Available evidence indicates that ozone therapy may serve as a valuable adjunct in the management of immunodeficiencies by modulating immune responses, reducing oxidative stress, and restoring homeostatic balance. Although current clinical outcomes are promising, further multicenter randomized trials are needed to standardize dosing protocols, assess long-term effectiveness, and confirm safety. Full article

The hypoxic, cold, and high-ultraviolet radiation environments at high altitude pose severe challenges to mammalian immune and metabolic systems. However, little is known about how captive forest musk deer adapt to high-altitude environments and their seasonal variations. This study analyzed peripheral blood transcriptomes of 33 captive forest musk deer (Moschus berezovskii) at high altitude (~3900 m) and low altitude (~1450 m) during autumn-winter and spring-summer seasons. Results revealed comprehensive immune suppression in the high-altitude group during autumn-winter (downregulation of complement system CFB/C2/C3, interferon pathway genes including FLT3, with only natural killer (NK) cell PRKCQ upregulated), coupled with energy-conserving metabolic reprogramming (altered carbohydrate metabolism, inhibited lipid synthesis, fat mobilization, suppressed protein degradation). During spring-summer, neutrophil antimicrobial responses (SLPI/NCF1/ELANE) and humoral immunity (B cell differentiation genes PAX5/RUNX1; class-switch enzyme AICDA) partially recovered while cellular immunity (IL15/B2M) remained suppressed, accompanied by enhanced anabolic metabolism and adipocyte differentiation. Notably, NK cell-mediated cytotoxicity showed selective enhancement despite comprehensive immune suppression, representing an energy-efficient innate defense strategy. This study provides the first characterization of seasonal immune dynamics in a high-altitude cervid species. These findings reveal persistent immune constraints in high-altitude populations and provide theoretical foundations for disease prevention and health management in captive forest musk deer at high altitudes. Full article

Interferons (IFNs) are well-known immunostimulants involved in both innate and adaptive immune responses. These multifunctional proteins mediate an early antiviral response and have pronounced immunomodulatory and antiproliferative properties. Due to their potency, IFNs have been used not only in the treatment of viral infections but also various other diseases. However, the use of IFNs in antitumor therapy has been limited by the frequent severe side effects, which reduced their appeal for the treatment of cancer. In this review, we focused on current data on recombinant IFNs used for anticancer therapy, as well as the development of promising IFN-based gene therapy approaches, with a focus on their safety and therapeutic efficacy. We also highlighted various types of IFNs and their application niches in the treatment of not only cancers in combination therapy but also of certain rare diseases. Taken together, this review improves our understanding of the existing IFN applications in cancer therapy, the disadvantages of using IFNs, and possible approaches for their improvement. Full article

Inborn errors of immunity (IEIs), formerly referred to as primary immunodeficiencies (PID), represent a heterogeneous group of hereditary disorders that significantly increase patients’ susceptibility to severe and recurrent infections. Toll-like receptors (TLRs) play a pivotal role in host defense as fundamental components of innate immunity, while also linking it to adaptive immune responses. This review summarizes advances in understanding the involvement of TLRs in the pathogenesis of IEIs in children. It highlights genetic defects such as deficiencies in MyD88, IRAK-4, NEMO, and TLR3, which lead to distinct clinical phenotypes, for example, increased susceptibility to bacterial infections or herpes simplex virus type-1 (HSV-1) encephalitis. The review also examines more complex disorders, including chronic granulomatous disease (CGD), common variable immunodeficiency (CVID), and X-linked agammaglobulinemia (XLA), in which TLR signaling may be either impaired or dysregulated. This analysis demonstrates the growing importance of functional assays evaluating TLR activity as a diagnostic tool complementary to genetic testing, as well as their potential to precisely characterize immunological phenotypes. Furthermore, current therapeutic perspectives are discussed, including the use of TLR agonists, which have shown promising results in oncology, the role of gene therapy as a causal treatment option, and a proposed diagnostic algorithm incorporating TLR-based evaluation. Despite significant progress, substantial knowledge gaps remain, particularly regarding the full spectrum of TLR signaling abnormalities across IEI subtypes. The conclusions emphasize the need for large-scale, international studies to achieve a comprehensive understanding of pathogenic mechanisms and to develop more targeted and effective therapeutic interventions for children affected by these rare disorders. Full article

Dendritic cells (DCs) are among the first immune cells to detect viral invasion and play a central role in initiating and shaping antiviral immune responses. Many innate and adaptive immune functions of DCs are regulated by cathepsins, proteolytic enzymes primarily found in acidic endolysosomal compartments. Different DC subsets exhibit distinct cathepsin expression patterns, influencing their functional capacities and interactions with viruses. In DCs, cathepsins contribute to virus sensing through innate receptors, regulate cytokine production and DC migration, and are essential for viral antigen degradation and loading onto MHC molecules for T-cell activation. Many viruses, however, have evolved mechanisms to alter cathepsin expression and activity, thereby subverting DC function and promoting their own persistence. Indeed, cathepsins can facilitate viral entry into DCs, promote viral replication, and support immune evasion strategies. In this review, we summarize recent advances in understanding the role of cathepsins in DC–virus interactions, emphasizing both how DCs exploit cathepsins to generate protective immune responses and how viruses manipulate cathepsin activity to their advantage. We particularly focus on clinically relevant viral pathogens, including HIV, influenza virus, hepatitis C virus, human cytomegalovirus, Ebola virus, and SARS-CoV-2, to illustrate the multifaceted influence of cathepsins on DC biology during viral infection. Full article

Radiotherapy remains a central component of cancer therapy that induces DNA damage and cancer cell death. Beyond its cytotoxic effects, radiotherapy acts as a potent immunomodulator by releasing immunogenic molecules, inflammatory mediators, and neoantigens that shape anti-tumor immunity. Radiation-induced immune responses can have opposing effects, including immune activation or immunosuppression that dictate local tumor responses. Increasing evidence suggests these immunologic effects are not confined to the site of irradiation, as radiation exposure to surrounding normal tissue can trigger systemic immune signaling that affects local tumor progression as well as metastatic spread. This review examines radiotherapy-induced immune responses across three interconnected contexts: (i) tumor-intrinsic signaling during radiation; (ii) tumor microenvironmental changes where innate and adaptive immune responses alter local outcomes; and (iii) systemic and off-target effects contributing to broader immune remodeling. A comprehensive understanding of radiotherapy-induced immune responses will guide therapeutic strategies to enhance its immunological potential while minimizing unintended immune and off-target effects. Full article

Background/Objectives: Cancer’s complexity can be rationalized through the “hallmarks of cancer,” which define the key biological capabilities driving malignancy. Induced hyperthermia—an adjunctive therapy that elevates body temperature above the normal setpoint for a defined period—has been explored for its modulatory effects on these hallmarks. This systematic review aims to evaluate the effects and mechanisms of induced hyperthermia on tumor cells through the established hallmarks of cancer framework. Methods: A systematic search following the Cochrane guidelines and PRISMA assessment tool was conducted in PubMed and Cochrane Library (2000–2025) to identify reviews on the effects of induced hyperthermia on cancer hallmarks. Studies’ predefined inclusion criteria were independently evaluated by two external teams and graded using PRISMA standards. Results: From the 2015 records screened, 103 studies met the inclusion criteria. Evidence indicates that induced hyperthermia modulates seven of the ten cancer hallmarks. The most well-supported mechanisms of action include (1) the immune system activation (39–41 °C)—enhancing antigen presentation, activating innate/adaptive immune cells, promoting tumor infiltration—and (2) genome instability and mutation (41 °C)—impairing DNA repair pathways and increasing tumor vulnerability. Both hallmarks provide evidence clarifying the mechanistic pathways through which induced hyperthermia exerts its effects. Conclusions: Induced hyperthermia exerts multifaceted, temperature-dependent effects on cancer biology, predominantly through immune activation and genomic destabilization. While it enhances the therapeutic sensitivity of other treatment modalities (e.g., chemotherapy, radiotherapy) and antitumor responses, excessive heating may induce immune suppression and thermotolerance. Optimizing temperature parameters and identifying biomarkers are essential for integrating hyperthermia into targeted and multimodal cancer therapies. Full article