Deciphering cross-cohort metabolic signatures of immune responses and their implications for disease pathogenesis.

The complex interplay between circulating metabolites and immune responses, which is pivotal to disease pathophysiology, remains poorly understood and understudied in systematic research. Here, we performed a comprehensive analysis of the immune response and circulating metabolome in two Western European cohorts (534 and 324 healthy individuals) and one from sub-Saharan Africa (323 healthy donors). At the metabolic level, our analysis revealed sex-specific differences in the correlation between phosphatidylcholine and cytokine responses following ex vivo stimulation.

A genome-wide association study identifies new loci associated with response to SARS-CoV-2 mRNA-1273 vaccine in a cohort of healthy healthcare workers.

Introduction: The COVID-19 pandemic had significant global public health consequences, affecting over 200 countries and regions by 2020. The development and efficacy of specific vaccines, such as the mRNA-1273 (Spikevax) vaccine developed by Moderna Inc., have substantially reduced the impact of the pandemic and mitigated its consequences.

Identification of four autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.

We investigated the influence of 55,583 autophagy-related single nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across four independent populations comprising 5,472 CLL cases and 726,465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the four populations identified, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (p=1.

Maladaptive trained immunity in viral infections.

Trained immunity (TRIM) is a form of long-lasting functional reprogramming of innate immune cells and their progenitors that enhances responsiveness to subsequent stimuli. Although first characterized in myeloid cells, TRIM was recently extended to nonmyeloid cell types, including endothelial and glial cells, which also exhibit stimulus-driven, memory-like behavior. While initially recognized as a protective mechanism, particularly in the context of vaccines and acute infections, TRIM can also become maladaptive, promoting chronic inflammation, immune dysfunction, and disease.

Can metaphors in patient information materials improve comprehension and attitudes regarding innovative treatment? The case of personalized immunotherapy for sepsis.

Objectives: Effective communication is essential for patients and their relatives to comprehend and accept novel treatments, such as personalized immunotherapy for sepsis in the ICU. However, communication in the ICU is challenging. Written information materials can supplement conversations with healthcare providers, enabling patients and their relatives to consult information later.

BCG-induced trained immunity potentiates TH17 responses in vitro.

Trained immunity amplifies innate immune responses in an antigen-independent manner. This study explored the ability of trained human primary macrophages to modulate the phenotype and function of T cells. Macrophages play an important role in antigen presentation, resulting in T-cell activation and antigen-specific clonal expansion; however, few studies have investigated whether trained immunity induction in macrophages modulates T cell activation.

The long-term effect of metabolic bariatric surgery on innate immune cell phenotype and function.

Objectives: Obesity is an important risk factor for atherosclerotic cardiovascular disease. This cardiovascular risk remains increased even after substantial weight loss by bariatric surgery. Innate immune cells are important regulators of atherogenesis and can adopt a long-term hyperinflammatory phenotype via epigenetic reprogramming, called "trained immunity".

Genetic and molecular landscape of comorbidities in people living with HIV.

People living with HIV (PLHIV) have an increased susceptibility to non-AIDS comorbidities. In this study, we systematically profiled 1,342 PLHIV across five omics layers and immune function. We found latent factors, resulting from integrating epigenomics, transcriptomics, proteomics, metabolomics and immune responses, linked to cardiovascular diseases, the presence of carotid plaque and chronic obstructive pulmonary disease in PLHIV.

Effects of simulated Martian environmental stressors on specific human pathogen-immune system interactions.

Unlabelled: The identification of health risks associated with long-term crewed missions to Mars is critical for mission planning and crew safety. Human-associated pathogens can be part of the microbiome and are likely to be transported during these missions. This study examines the immunological responses of human immune cells stimulated with non-fastidious bacterial species that cause opportunistic infections, i.

Development and validation of an interpretable machine learning model for retrospective identification of suspected infection for sepsis surveillance: a multicentre cohort study.

Background: How to identify suspected infection for sepsis surveillance purposes remains a well-recognised challenge. This study aimed to operationalise suspected infection for sepsis surveillance by developing an interpretable machine learning (ML) model for retrospective identification of patients with sepsis.

Methods: This multicentre cohort and machine learning study was conducted in two Dutch tertiary care hospitals.

Long-term effects of BCG vaccination on telomere length and telomerase activity.

This study explores the effects of Bacillus Calmette-Guérin (BCG) vaccination on telomere maintenance, an aging-related process, in immune cells. While BCG reduces systemic inflammation and enhances innate immune responsiveness by inducing trained immunity, its effects on other immune aging hallmarks, such as telomere shortening, are not fully understood. We assessed telomere length in two independent human cohorts before and three months after BCG vaccination.

Metabolic imprinting drives epithelial memory during mucosal fungal infection.

Epithelial cells at barrier sites are emerging as active participants in innate immune memory, yet the underlying metabolic and epigenetic mechanisms remain unclear. Here, we uncover a previously unrecognized form of trained immunity in oral epithelial cells that enhances protection against fungal infection. Using a mouse model, we show that mucosal exposure to confers sustained protective memory that is independent of adaptive immunity and myeloid cells.

Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions.

Deciphering the intricate regulatory mechanisms underlying biological processes holds promise for elucidating how genetic variants contribute to immune-related disorders. We map genetic effects on gene expression (expression quantitative trait locus, eQTL) using single-cell transcriptomes of 152 samples from 38 healthy individuals, covering baseline state and lipopolysaccharide challenge either before or after Bacillus Calmette-Guerin vaccination. Interestingly, we uncover a monocyte eQTL linked to the LCP1, shedding light on inter-individual variations in trained immunity.

Sex-specific DNA methylation associations with circulating urate levels and BCG-induced urate changes.

Background: Urate concentration and the physiological regulation of urate homeostasis exhibit clear sex differences. DNA methylation has been shown to explain a substantial proportion of serum urate variance, mediate the genetic effect on urate concentration, and co-regulate with cardiometabolic traits. However, whether urate concentration is associated with DNA methylation in a sex-dependent manner is unknown.

Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis.

This study examines the role of host inflammation in the high mortality of tuberculous meningitis (TBM) and identifies potential biomarkers associated with improved survival. We conducted a case-control study involving 131 patients in a discovery cohort, 81 TBM patients in a validation cohort, and 43 non-infected controls from a referral hospital in Indonesia. We measured 94 inflammation-related proteins in cerebrospinal fluid (CSF) and performed genome-wide quantitative trait loci (QTL) mapping.

A dual nature of γδ T cell immune memory responses.

Immune memory was considered for decades an exclusive hallmark of the adaptive immune response. However, recent studies have revealed that innate immune cells can also 'recall' information of a primary insult during infection or vaccination and deploy robust antigen-agonistic immune reactivity upon secondary challenge. This innate immune memory response is designated as 'trained immunity'.

Metabolic dysregulation of trained immunity in immune aging and the impact of dietary patterns.

Trained immunity (TRIM) is the process through which the innate immune system undergoes memory-like epigenetic and metabolic reprogramming following an earlier infectious challenge. Trained immunity can be induced, in a similar fashion to microbial structures, by various endogenous compounds: oxidized low-density lipoproteins, lipoprotein(a), glucose and uric acid, and monosodium urate. Lipids, glucose, and protein metabolic dysfunction have the potential to perpetuate a proinflammatory feedback loop through the induction of maladaptive trained immunity programs, as shown in cardiovascular diseases, diabetes, and hyperuricemia.

Interferon gamma rebalances immunopathological signatures in Chronic Granulomatous Disease through metabolic rewiring.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent life-threatening infections and hyperinflammatory complications. It is caused by mutations in the NADPH oxidase complex and the consequent loss of reactive oxygen species (ROS) production. Recombinant human interferon gamma (rIFN-γ) prophylaxis reduces the risk of severe infections, but the mechanisms behind its efficacy in CGD are still an open question, as it does not restore NADPH oxidase-dependent ROS production.

Engineering Fusion Proteins for Nanomedicine-Based Cytokine Therapy.

Cytokines play a crucial role in cell communication and immunity, making them interesting potential therapeutics for immune-mediated conditions. However, cytokine therapeutics' clinical translation is hampered by their short blood half-lives and unfavorable biodistribution, resulting in toxicity and poor pharmacokinetics. In this study, we present a strategy to improve cytokines' pharmacokinetic profile by engineering fusions of apolipoproteins and cytokines, which are formulated into apolipoprotein-based nanoparticles (cytokine-aNPs).

From losing control to regaining control: Patient experiences of care for Staphylococcus aureus bacteremia.

Objectives: Recommendations for appropriate Staphylococcus aureus bacteremia (SAB) care almost exclusively focus on preventing disease-specific outcomes like metastatic infection, relapse and mortality, rather than providing practical information on how to achieve person-centered care (PCC). We described characteristics and features of SAB care from a patient perspective and explored experiences regarding this care to formulate concrete recommendations for improving PCC in SAB patients.

Methods: One-time, in-depth, semi-structured, qualitative interviews with SAB patients ∼12 weeks post-SAB-diagnosis were conducted, including relatives if desired.

Long-term DNA methylation changes mediate heterologous cytokine responses after BCG vaccination.

Background: Epigenetic reprogramming shapes immune memory in both innate (trained immunity) and adaptive immune cells following Bacillus Calmette-Guérin (BCG) vaccination. However, the role of dynamic DNA methylation changes in post-vaccination immune responses remains unclear.

Results: We established a cohort of 284 healthy Dutch individuals, profiling genome-wide DNA methylation and cytokine responses to ex vivo stimulation at baseline, 14 days, and 90 days post-BCG vaccination.

Microbial-induced trained immunity for cancer immunotherapy.

Myeloid innate immune cells, including macrophages, neutrophils, myeloid-derived suppressor cells, and dendritic cells, represent major components of the tumor microenvironment (TME), exhibiting remarkable plasticity and dual roles in cancer progression and immune regulation. In recent years, microbial-induced innate immune memory, also termed "trained immunity" (TRIM), has emerged as a novel strategy to reprogram myeloid cells into an immunostimulatory, antitumor state. In this review, we explore the intricate landscape of myeloid cells in cancer and examine how microbial ligands, such as the Bacillus Calmette-Guérin vaccine and β-glucan, reprogram both bone marrow progenitors and tissue-resident myeloid cells to enhance inflammatory and antitumor responses.

Trained Immunity Induced by Oxidized Low-Density Lipoprotein Is Dependent on Glutaminolysis.

Atherosclerosis is a chronic inflammatory disease of the arterial wall that causes cardiovascular disease. Monocyte-derived macrophages are an important contributor to atherogenesis. Monocytes can become primed for higher responsiveness to secondary, unrelated stimuli-a phenomenon known as trained immunity-a process driven by intracellular metabolic and epigenetic reprogramming.

Immunomodulatory function of chitosan is dependent on complement receptor 3.

Chitosan, the deacetylated product of chitin, is a significant component of the cell walls of nearly all fungi. In contrast with the high level of attention paid to plant immune recognition of chitin and chitosan of plant pathogenic fungi we know much less about the mammalian immune system immune recognition of chitosan during infections by human pathogenic fungal species. Here we show that the mammalian β-integrin CR3 complement scavenger receptor, that is expressed on monocytes and macrophages, recognises chitosan from a range of fungal sources and that this leads to the secretion of IL-6, IL-1β and TNF.