Inflammation and Regeneration, Год журнала: 2025, Номер 45(1)
Опубликована: Июнь 3, 2025
Язык: Английский
Nature Immunology, Год журнала: 2024, Номер 25(5), С. 847 - 859
Опубликована: Апрель 24, 2024
Abstract Immune cells need to sustain a state of constant alertness over lifetime. Yet, little is known about the regulatory processes that control fluent and fragile balance called homeostasis. Here we demonstrate JAK-STAT signaling, beyond its role in immune responses, major regulator cell We investigated JAK-STAT-mediated transcription chromatin accessibility across 12 mouse models, including knockouts all STAT factors TYK2 kinase. Baseline signaling was detected CD8 + T macrophages unperturbed mice—but abrogated unstimulated deprived their normal tissue context. observed diverse gene-regulatory programs, effects STAT2 IRF9 were independent STAT1. In summary, our large-scale dataset integrative analysis mutant wild-type mice uncovered crucial cells, where it contributes poised epigenetic transcriptional helps prepare these for rapid response stimuli.
Язык: Английский
Процитировано
31
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 2, 2025
Abstract Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained IFN-γ-independent adaptive immune response, or effective innate host clearing Mycobacterium (Mtb) without immunity. In Indonesian household contacts (n = 1347), persistently IGRA negative status was associated with presence of BCG scar, and - especially among those scar altered cells dynamics, higher heterologous ( Escherichia coli -induced) proinflammatory cytokine production, inflammatory proteins in the mitogen tube. Neither circulating concentrations Mtb -specific antibodies nor functional antibody activity at baseline follow-up. cohort adults low incidence setting, vaccination induced but only marginally affected Mtb- profiles. Our findings suggest that more efficient rather than humoral mediates early clearance . The protective effect against infection may linked priming, also termed ‘trained immunity’.
Язык: Английский
Процитировано
3
Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(7), С. 643 - 661
Опубликована: Май 24, 2024
Abstract By binding to multiple antigens simultaneously, multispecific antibodies are expected substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass constructs, consist engineered structures designed bridge immune effector cells their target, thereby redirecting response toward tumor or infected cells. The increasing number recent clinical trials evaluating engagers reflects important role these molecules in new therapeutic approaches for cancer infections. In this review, we discuss how different types (T natural killer lymphocytes, as well myeloid cells) can be bound by immunotherapy infectious diseases. Furthermore, explore preclinical advancements challenges translating current knowledge from virology field. Finally, speculate on promising future directions that may take treatment antiviral therapy.
Язык: Английский
Процитировано
17
Clinical Immunology, Год журнала: 2024, Номер 261, С. 109930 - 109930
Опубликована: Фев. 9, 2024
While the efficacy of many current vaccines is well-established, various factors can diminish their effectiveness, particularly in vulnerable groups. Amidst emerging pandemic threats, enhancing vaccine responses critical. Our review synthesizes insights from immunology and epidemiology, focusing on concept trained immunity (TRIM) non-specific effects (NSEs) that confer heterologous protection. We elucidate mechanisms driving TRIM, emphasizing its regulation through metabolic epigenetic reprogramming innate immune cells. Notably, we explore extended protective scope like BCG COVID-19 against unrelated infections, underscoring role reducing neonatal mortality combating diseases malaria yellow fever. also highlight novel strategies to boost efficacy, incorporating TRIM inducers into formulations enhance both specific responses. This approach promises significant advancements development, aiming improve global public health outcomes, especially for elderly immunocompromised populations.
Язык: Английский
Процитировано
10
Cell, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Язык: Английский
Процитировано
2
Clinical & Translational Immunology, Год журнала: 2025, Номер 14(1)
Опубликована: Янв. 1, 2025
Abstract Objectives Bacille Calmette–Guérin (BCG) vaccination has off‐target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed determine the immunomodulatory of BCG vaccines against SARS‐CoV‐2. Methods Blood samples, from a subset 275 SARS‐CoV‐2‐naïve healthcare workers randomised (BCG group) or no (Control in BRACE trial, were collected before 28 days after primary course (two doses) ChAdOx1‐S (Oxford‐AstraZeneca) BNT162b2 (Pfizer‐BioNTech) vaccination. SARS‐CoV‐2‐specific antibodies measured using ELISA multiplex bead array, whole blood cytokine γ‐irradiated SARS‐CoV‐2 (iSARS) stimulation by T‐cell activation‐induced marker intracellular staining assays. Results After randomisation (mean 11 months) but prior COVID‐19 vaccination, group had lower iSARS than Control group. two doses ChAdOx1‐S, differences iSARS‐induced between found three cytokines (CTACK, TRAIL VEGF). No groups There also vaccine‐induced antigen‐specific antibody responses, activation production. Conclusion induced broad persistent reduction ex vivo Following this effect was abrogated, did not influence adaptive vaccine antigens.
Язык: Английский
Процитировано
1
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Май 19, 2025
Introduction BCG vaccination can have heterologous or non-specific effects (NSE) that confer resistance against pathogens other than its target Mycobacterium tuberculosis, but the underlying mechanisms are not fully understood. Methods We conducted a systematic review synthesising existing literature on immune mediating heterologous/NSE of BCG. Searches were using MEDLINE and Scopus. Results 1032 original records identified, which 67 deemed eligible. Several potentially relevant pathways although there may be variation by pathogen. Recent studies focused trained immunity whereby innate cells, hematopoietic stem progenitor cells from they derived, undergo epigenetic metabolic reprogramming allowing them to respond more effectively antigen exposures unrelated stimulus. However, processes such as granulopoiesis cross-reactive adaptive also play role. Heterologous NSEs influenced several endogenous exogenous variables. Discussion discuss quality available data, importance understanding protection, implications for strategies. Systematic registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42023400375 , identifier CRD42023400375.
Язык: Английский
Процитировано
1
Vaccine, Год журнала: 2024, Номер 42(24), С. 126109 - 126109
Опубликована: Июль 8, 2024
The Bacille Calmette-Guerin (BCG) vaccine is a well-established inducer of innate immune memory (also termed trained immunity), causing increased cytokine production upon heterologous secondary stimulation. Innate responses are known to be influenced by season, but whether seasons impact induction immunity not known. To explore the influence season on induced BCG vaccine, we vaccinated healthy volunteers with either during winter or spring. Three months later, measured ex vivo against stimuli, analyzed gene expressions and epigenetic signatures cells, compared these baseline before vaccination. vaccination stronger increase in pro-inflammatory cytokines peripheral blood mononuclear cells (PBMCs) stimulation different bacterial fungal In contrast, resulted lower IFNγ release PBMCs spring Furthermore, NK winter-vaccinated people had greater capacity only minor effects transcriptome monocytes 3 later. identified season-dependent changes vaccination, partly explaining higher cell reactivity group. These results suggest that more prone induce robust response activating reprogramming especially cells. (Dutch clinical trial registry no. NL58219.091.16)
Язык: Английский
Процитировано
5
The Lancet Infectious Diseases, Год журнала: 2024, Номер unknown
Опубликована: Сен. 1, 2024
Язык: Английский
Процитировано
4
Immunology Letters, Год журнала: 2024, Номер 267, С. 106851 - 106851
Опубликована: Март 11, 2024
Bacillus Calmette–Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called trained immunity mediated by epigenetic metabolic reprogramming. Cholesterol synthesis plays an amplifying role through mevalonate release. Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, can inhibit cholesterol synthesis. We explored effects on induced BCG placebo-controlled clinical study (NL74082.091.20) young, healthy individuals. Participants receiving single-dose oral alendronate the day of had more neutrophils plasma one month after treatment. Alendronate led to reduced proinflammatory cytokine production PBMCs stimulated with heterologous bacterial viral stimuli later. Furthermore, addition transcriptionally suppressed multiple response pathways upon stimulation. Our findings indicate that N-BPs modulate long-lasting capacity cells.
Язык: Английский
Процитировано
3