Finding the best way to train the immune system against lymphoma.
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Antigens, Neoplasm↗
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Results for “Trained Immunity”
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Convergent evolution of immune evasion in ESKAPE pathogens: A cross-pathogen architecture of conserved host-defense checkpoints.
Antimicrobial resistance in ESKAPE pathogens is primarily attributed to resistance genes, yet persistent infections despite appropriate therapy implicate immune evasion as an independent driver of treatment failure. Although immune-evasion mechanisms have been extensively characterized in individual pathogens, their shared architecture across the ESKAPE group remains insufficiently integrated. This review synthesizes current evidence to show that phylogenetically diverse ESKAPE pathogens have convergently evolved conserved strategies to evade host immunity under comparable selective pressures. A cross-pathogen immune-evasion framework emerges, encompassing impaired pathogen recognition, complement inhibition, phagocyte dysfunction, immunometabolic reprogramming, biofilm-mediated protection, and persistence-promoting inflammation, together with pathogen-specific virulence mechanisms. These processes intersect with adaptive immune dysfunction and emerging concepts, including quorum-sensing-mediated immunomodulation, trained immunity, and the itaconate-succinate immunometabolic axis, forming an interconnected persistence network rather than isolated virulence traits. This systems-level perspective identifies conserved host-directed therapeutic targets that may complement conventional antimicrobial therapy across species. However, host-directed therapies, immunotherapeutics, and vaccines remain largely preclinical or have shown inconsistent clinical efficacy. Mechanistic evidence is strongest for Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, whereas substantial knowledge gaps persist for Enterococcus faecium, Acinetobacter baumannii, and Enterobacter spp. Overcoming persistent ESKAPE infections will require targeting conserved host-pathogen interactions alongside pathogen-specific antimicrobial resistance mechanisms.
Convergent immune evasion↗
Epigenetic Gene Networks Governing Immune State Transitions Across the Lifespan.
Immune function across development, tissue repair, aging, and disease depends not only on signaling pathways but also on epigenetic architectures that determine whether coordinated transcriptional programs can be accessed and resolved. Increasing evidence indicates that epigenetic gene networks regulate the accessibility and reversibility of semi-stable immune states, shaping plastic, homeostatic, reparative, and degenerative configurations. We propose the concept of epigenetic transition windows, defined as temporally and contextually restricted intervals during which epigenetic constraints are relaxed, permitting coordinated and reversible transitions between immune states. During development, these windows are broad and support immune tolerance and adaptive plasticity. In adulthood they become spatially and temporally restricted, preserving stability while enabling conditional adaptation. With aging, they progressively narrow, contributing to chronic inflammation, impaired repair, and increased vulnerability to neurodegeneration. Conversely, pathological persistence of regulatory permissiveness may underlie immune evasion and sustained plasticity in cancer. We outline operational genomic readouts for quantifying transition windows, including chromatin accessibility variance, enhancer switching dynamics, reversibility metrics, and cross-cell coordination indices, and derive experimentally testable predictions that distinguish this model from pathway-centric or damage-centric explanations. By reframing immune dysfunction as a failure of regulated state transition rather than excessive signaling alone, this framework integrates inflammaging, trained immunity, immune resolution failure, and tumor immune escape within a unified regulatory architecture and provides a systems-level perspective on immune adaptability across the lifespan.
Epigenesis, Genetic↗
The TRIM-cancer paradox: BCG as a programmable vaccine platform and a mechanistic probe for rational immunotherapy design.
BCG, a first-generation live vaccine, is being reconsidered as an immunological platform. Interest in its heterologous protection intensified during the pandemic. However, large-scale clinical trials revealed inconsistencies in the efficacy of native BCG. This review argues that BCG's main value lies in its potential as a modifiable vector platform and in its ability to reveal tractable molecular pathways for therapeutic design. This review summarizes the molecular basis of BCG-induced trained immunity (TRIM), focusing on PRR-driven signaling, metabolic rewiring, and epigenetic remodeling in innate immune cells and hematopoietic progenitors. It also maps their convergence with pathways that sustain pro-tumorigenic inflammation. The original conceptual paradigm of the "TRIM-Cancer Paradox" is presented. This paradigm posits that the same innate immune circuits that mediate protective heterologous responses can drive tumor-promoting inflammation and immune escape under conditions of chronic dysregulation. Recombinant BCG (rBCG) is further analyzed as a strategy to rationally amplify or redirect these circuits, the current clinical landscape of BCG-based interventions across various diseases and oncological malignancies is highlighted, and specific molecular nodes that could be exploited to increase the precision, efficacy, and safety of rBCG-based therapies are identified. Overall, this review proposes BCG a programmable immunological platform and to use the TRIM-Cancer Paradox as a novel design principle for next-generation rBCG platforms that transcend traditional vaccinology and cancer immunotherapy applications.
Humans↗
A training procedure for immunization.
A booklet on child immunization and a training procedure using a video have been developed in a health authority. The initiative has proven highly acceptable and has resulted in a demonstrable increase in professional knowledge and in vaccine uptake. Further initiatives are described.
Child↗
Chronic exercise training effects on immune function.
PURPOSE: This paper reviews the recent literature on the chronic effects of exercise training on immune function in humans. There is a general perception by athletes and other physically active individuals that regular moderate activity enhances, whereas intense exercise suppresses, resistance to minor illnesses such as upper respiratory tract infection (URTI). This perception is supported by epidemiological data in endurance athletes and limited data from intervention studies using moderate exercise in previously untrained individuals. The apparently high incidence of URTI among endurance athletes has prompted interest the relationship between chronic exercise training and immune function. Whereas immune cell number is generally normal during intense exercise training, recent evidence suggests that prolonged periods of intense training may lead to slight impairment in immune parameters such as neutrophil function, serum and mucosal immunoglobulin levels, plasma glutamine concentration, and possibly natural killer cell cytotoxic activity. In contrast. moderate exercise training has either no effect on, or may stimulate, these immune parameters. CONCLUSION: Whereas athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to minor illnesses such as URTI. Strategies to prevent URTI in athletes include avoiding overtraining, providing adequate rest and recovery during the training cycle and after competition, limiting exposure to sources of infection, ensuring adequate nutrition, and possibly vitamin C supplementation. It is uncertain at present whether moderate exercise training is helpful in preventing infectious illness among the wider population.
Antibody Formation↗
Multilevel Proteomics Reveals Epigenetic Signatures in BCG-Mediated Macrophage Activation.
The bacillus Calmette-Guérin BCG vaccine (Mycobacterium bovis) is primarily used to prevent tuberculosis (TB) infections but has wide-ranging immunogenic effects. One of its most notable properties is its ability to induce trained immunity, a memory-like response in innate immune cells such as macrophages. Through targeted analyses of well-established histone marks, prior research has shown that these changes are generated through epigenetic modification. Mass spectrometry-based proteomic approaches provide a way to globally profile various aspects of the proteome, providing data to further identify unexplored mechanisms of BCG-mediated immunomodulation. Here we use multi-level proteomics (total, histone, and phospho to identify networks and potential mechanisms that mediate BCG-induced immunomodulation in macrophages. Histone-focused proteomics and total proteomics were performed at the University of Cape Town (data available via ProteomeXchange with identifier PXD051187), while phosphoproteomics data was retrieved from the ProteomeXchange Repository (identifier PXD013171). We identify several epigenetic mechanisms that may drive BCG-induced training phenotypes. Evidence across the proteomics and histone-focused proteomics data set pair 6 epigenetic effectors (NuA4, NuRD, NSL, Sin3A, SIRT2, SIRT6) and their substrates.
Epigenesis, Genetic↗
Qi-training (qigong) enhanced immune functions: what is the underlying mechanism?
The authors observed that Qi-training enhances immune function and modulates neurohormone concentrations. The exact signal and priming mechanism for enhanced neutrophil function by Qi-training has not yet been demonstrated. This study investigated the effect of Qi-training on intracellular signaling leading to the enhancement of immune function. The growth hormone (GH) concentrations and O2- production by neutrophils (PMNs) was significantly increased after 1 h of Qi-training compared with the basal state. To verify that endogenous GH mediates the priming of PMNs, serum obtained from elderly subjects in the basal state and after Qi-training was incubated with neutrophils isolated from young subjects for 60 min and triggered with N-formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP). Significant O2- production was observed in the PMNs incubated with serum collected after a Qi-training (p < .05). On the other hand, the priming effect on the PMNs was abolished in Qi-training sera depleted of endogenous GH with anti-human GH polyclonal antibody (p < .01) and the tyrosine kinase inhibitor, genistein (p < .01). The authors suggest that the endogenous GH released during and immediately after Qi-training mediates the priming events through tyrosine kinase activation in PMNs.
Adult↗
School-based immunization clinics. A method for raising community immunization levels.
A survey in ten Sacramento schools indicated that immunization levels were low and that they compared with the low levels estimated by the Center for Disease Control for the rest of the country. The problem was given priority, and a plan evolved using the community's schools.A method was developed to screen and immunize large numbers of children in a short time. The schools were used as a focal point to immunize both school-aged and preschool-aged children in each section of Sacramento County. A trained immunization team carried out immunizations with high cost effectiveness.
California↗
Effect of 8 wk of bicycle training on the immune system of patients with rheumatoid arthritis.
The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity. Maximal O2 uptake increased significantly, whereas heart rate at stage 2 and rate of perceived exertion decreased significantly, in the training group compared with the controls. Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training. Training did not induce changes in blood mononuclear cell subpopulations, proliferative response, or natural killer cell activity. Furthermore the plasma concentrations of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 did not change in response to training. It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis.
Aged↗
The IL-1 system in inflammation and cancer.
Inflammation is a pathogenetic driver of several pathological conditions, including cancer. The tumor microenvironment, which includes cellular, molecular, and structural components, is an essential component of cancer, involved in tumor promoting or controlling processes. In particular, inflammatory players contribute to the establishment of a tumor-promoting microenvironment, which affects all stages of tumor development, from initiation to metastasis, as well as response to therapy. The IL-1 system includes two large sets of structurally related ligands and receptors, with agonist or regulatory activity, playing non-redundant roles in inflammation and immunity. Each of them has specific functions in tissue homeostasis, inflammation, innate and adaptive immune responses, and potentially contributes to processes related to carcinogenesis and metastasis, or immune-mediated control of cancer cells. Depending on the context and cellular target, IL-1 family members may play dual roles in cancer, driving both pro- or anti-tumor processes. IL-1α and IL-1β can directly promote cancer cell proliferation, survival, and plasticity, in addition to contribute to the establishment of a pro-inflammatory environment that promotes tissue remodeling, cellular stress responses, and genomic instability. On the other hand, IL-1 is a lymphoproliferative and activating molecule in innate and adaptive responses, thus contributing to anti-tumor immune mediated responses. In addition, members of the IL-1 system act as regulators of mechanisms involved in cancer, including emergency hematopoiesis, trained immunity, and metabolism. Here, we will provide an overview of the IL-1 system in cancer and discuss the functional complexity of IL-1 family cytokines, which orchestrate both protective and pro-tumorigenic responses, by directly acting on cancer cells and by driving environmental stimuli which indirectly act on cancer cells.
Humans↗
Single-cell transcriptional profiling identifies the swimming crab Portunus trituberculatus in response to bacterial infection.
Crustaceans rely entirely on innate immunity, yet the cellular composition, functional specialization, and pathogen-induced remodeling of their immune system remain poorly resolved. Here, we generated a high-resolution single-cell transcriptomic atlas of hemocytes from the swimming crab Portunus trituberculatus following Vibrio parahaemolyticus infection using 10× Genomics scRNA-seq. Seven putatively distinct hemocyte clusters were identified, including granulocytes, semigranular hemocytes, prohemocytes, unresolved hemocytes, hyalinocyte-like hemocytes, biosynthetically active secretory hemocytes, and regulatory hemocytes. Although the overall cellular composition remained relatively stable after infection, hemocytes exhibited pronounced cluster-specific transcriptional reprogramming involving Toll/NF-κB signaling, antimicrobial peptide synthesis and metabolic rewiring. By integrating single-cell and bulk transcriptomes, we identified multiple anti-lipopolysaccharide factors (ALFs) as key secretory effectors and experimentally validated their antibacterial activities. FITC-based bacterial engulfment assays and RNA-seq of sorted phagocytes demonstrated that phagocytic capability was shared across multiple hemocyte clusters. Notably, the immunoglobulin superfamily receptor DSCAM displayed extensive alternative splicing and strong infection-induced activation in unresolved hemocytes. Immune-training experiments showed that prior bacterial exposure was associated with altered DSCAM expression and reduced early cumulative mortality upon secondary challenge, suggesting a memory-like immune phenotype. These findings provide a foundational framework for understanding crustacean immunity and advancing disease-resistant breeding in aquaculture.
Antimicrobial peptides↗
Ensuring vaccine safety in immunization programmes--a WHO perspective.
Ever since vaccines were firstly used against smallpox, adverse events following immunization have been reported. As immunization programmes expand to reach even the most remote communities in the poorest countries, it is likely that many more events will be temporally linked with vaccine administration. Furthermore, the profound shift in the general public and media interest in adverse events may lead to undue concerns and allegations which may ultimately jeopardize immunization programmes world-wide. While the health professional has understood this issue for some time, the public and the media have now also become all too aware of the significance of vaccine-related adverse events. The familiar vaccines, well-tested over decades, have not changed--but the perception regarding their safety has shifted. Claims outrageous or reasonable are being made against both the old and the newly-introduced vaccines. At the same time, the immunological and genetic revolution of the last decade may well bring to our notice some hypothetical risks that need to be addressed at pre-clinical level. WHO has been at the leading edge to guarantee vaccine safety for the last 30 years and will continue to do so. The Organization's plans for the next decade and beyond include the Safe Injection Global Network (SIGN), the development and introduction of safer technologies, and the prevention, early detection and management of AEFIs. The new technologies include needle-containing injection devices such as the autodisable syringe, as well as mucosal and transcutaneous immunization. Training will continue to be at the centre of WHO's efforts, limiting human error to a minimum. Mechanisms have been set in place to detect and respond to new and unforeseen events occurring. Above all, there is a willingness to respond to new climates and new technologies so that the Organization is in the best position to ensure safe immunization for all the world's children.
Drug Contamination↗
Training and natural immunity: effects of diets rich in fat or carbohydrate.
The purpose of the study was to investigate whether a carbohydrate-rich versus fat-rich diet influenced the effect of training on the immune system. Ten untrained young men ingested a carbohydrate-rich diet [65 energy percent (E%) carbohydrate] and ten subjects a fat-rich diet (62E% fat) while endurance training was performed 3-4 times a week for 7 weeks. Maximal oxygen uptake increased by 11% in both groups. Blood samples for immune monitoring were collected before and at the end of the study. Blood samples were also collected, in parallel, from 20 age-matched subjects, and data from these subjects were used to eliminate day-to-day variation in the immunological tests. Independently of diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK) cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell activity, either unstimulated or stimulated with interleukin (IL)-2 or interferon (IFN)-alpha, did not change. Furthermore, training did not influence the percentages of CD3+, CD4+, CD8+, CD19+ or CD14+ cells. However, when the two diet groups were compared, it was found that the NK-cell activity had increased in the group on the carbohydrate-rich diet [from 16 (3)% to 27 (2)%] and decreased in the group on the fat-rich diet [from 26 (2)% to 20 (4)%] in response to training. The effect of training on unstimulated NK-cell activity was significantly different between the groups (P = 0.007). These data indicate that diet manipulation during training may influence natural immunity, and suggest that ingestion of a fat-rich diet during training is detrimental to the immune system compared to the effect of a carbohydrate-rich diet.
Adult↗
Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.
BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.
Humans↗
Prevention of work-related disability.
INTRODUCTION: The cost of work-related injury is large and is rising in many states. Managed care providers are being asked to assist with solutions, particularly in the area of facilitating return to work. Kaiser Permanente of the Northwest responded by developing the Kaiser on-the-job program, which includes processes to facilitate the primary, secondary, and tertiary prevention of work-related disability. METHODS: This paper describes the role that managed care can play in the prevention of work-related disability through consultation, training, immunization programs, and targeted screening and case management interventions. A quality and case management system is described, which gives physicians feedback on modified work and time-off authorization by diagnosis. RESULTS: The results demonstrate statistically significant decreasing physician-authorized average time loss for low back cases from 1991 through 1995 (17.8 disability days per case in 1991 and 15 per case in 1995, P = .01). According to Oregon State Accident Insurance Fund (SAIF Corporation) data, the Kaiser on-the-job average total claims cost was reduced 33% for disabling cases as compared to two other health care organizations (P = .002). CONCLUSION: The methods utilized here to prevent work-related disability appear effective. They are relevant to many managed care program models and their efforts to improve workplace health and productivity.
Accidents, Occupational↗
Effects of resistance training on resting immune parameters in women.
The aim of this investigation was to determine whether intense resistance training of 6 months duration influenced resting immune parameters. Previously untrained women underwent one of four training programs or were non-training controls (CON, n=7). The resistance-training groups trained for total body power (TP, n=16), total body hypertrophy (TH, n=18), upper body power (UP, n=15) or upper body hypertrophy (UH, n=15). Immune parameters were measured from a fasting morning blood draw in September/October (0 months, t(0)), November/December (3 months, t(3)), and April/May (6 months, t(6)). Lymphocyte subsets [CD4+ T cells, CD8+ T cells, natural killer cells (NK), and B cells], and mitogen-stimulated proliferation were measured. The concentration of NK cells increased ( P<0.001) after 3 months of training for the resistance-training groups but not the CON group. This increase was not present after 6 months of training, thus it was a transient change. Lymphocyte proliferation responses were similar across time for the resistance-trained and CON groups for all stimulation conditions. Thus, resistance training induces a transient increase in NK cells but has little effect on lymphocyte trafficking or proliferation. This was consistent despite differences in the volume of muscle mass trained or the manner of training (power verses hypertrophy).
Adolescent↗
The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones.
BACKGROUND: A decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed. RESULTS: Elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels were significantly lower than their sedentary peers. They also showed significantly lower IL-3 production in comparison to sedentary elderly subjects but similar to the youngs. Anabolic hormone levels did not differ between elderly groups and no clear correlation was found between hormones and cytokine levels. CONCLUSION: Highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function but not the deterioration in endocrine function.
Journal Article↗