Trained immunity in chronic inflammatory diseases and cancer

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Language: Английский

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Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(7), P. 643 - 661

Published: May 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.

Language: Английский

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Friends to remember: innate immune memory regulation by the microbiota

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Genetic and epigenetic dysregulation of innate immune mechanisms in autoinflammatory diseases

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(20), P. 4414 - 4432

Published: March 12, 2024

Dysregulation and hyperactivation of innate immune responses can lead to the onset systemic autoinflammatory diseases. Monogenic diseases are caused by inborn genetic errors based on molecular mechanisms at play, be divided into inflammasomopathies, interferonopathies, relopathies, protein misfolding, endogenous antagonist deficiencies. On other hand, more common multifactorial, with both non‐genetic factors playing an important role. During last decade, long‐term memory characteristics have been described (also called trained immunity) that in physiological conditions provide enhanced host protection from pathogenic re‐infection. However, if dysregulated, induction immunity become maladaptive, perpetuating chronic inflammatory activation. Here, we describe epigenetic dysregulation system maladaptive leads perpetuation most recently

Language: Английский

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Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 29, 2024

For decades, innate immune cells were considered unsophisticated first responders, lacking the adaptive memory of their T and B cell counterparts. However, mounting evidence demonstrates surprising complexity immunity. Beyond quickly deploying specialized initiating inflammation, two fascinating phenomena – endotoxin tolerance (ET) trained immunity (TI) have emerged. ET, characterized by reduced inflammatory response upon repeated exposure, protects against excessive inflammation. Conversely, TI leads to an enhanced after initial priming, allowing system mount stronger defences subsequent challenges. Although seemingly distinct, these may share underlying mechanisms functional implications, blurring lines between them. This review will delve into ET TI, dissecting similarities, differences, remaining questions that warrant further investigation.

Language: Английский

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Integrated organ immunity: a path to a universal vaccine

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(2), P. 81 - 82

Published: Jan. 11, 2024

Language: Английский

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Symbiosis takes a front and center role in biology

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(4), P. e3002571 - e3002571

Published: April 5, 2024

All animals and plants likely require interactions with microbes, often in strong, persistent symbiotic associations. While the recognition of this phenomenon has been slow coming, it will impact most, if not all, subdisciplines biology.

Language: Английский

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High-throughput screen identifies non inflammatory small molecule inducers of trained immunity

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(29)

Published: July 8, 2024

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result increased cytokine effector responses pathogenic challenges, providing nonspecific protection against disease. It may also improve immune established immunotherapeutics vaccines. Despite its promise for next-generation therapeutic design, most current understanding experimentation conducted with complex heterogeneous biologically derived molecules, such as β-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. limited collection of training compounds limits study genes involved each molecule has both nontraining effects. Small molecules tunable pharmacokinetics delivery modalities would assist trained future applications. To identify small inducers immunity, we screened a library 2,000 drugs drug-like compounds. Identification well-defined our innate memory broaden scope clinical We identified over two dozen several chemical classes that induce phenotype absence initial activation—a limitation reported training. A surprising was identification glucocorticoids, traditionally considered immunosuppressive, an unprecedented link between glucocorticoids immunity. chose seven these top candidates characterize establish activity vivo. In this work, expand number known creating alternative avenues studying applying

Language: Английский

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Antigen-presenting innate lymphoid cells induced by BCG vaccination promote a respiratory antiviral immune response through the skin‒lung axis

Cellular and Molecular Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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Immune training enhances anti-viral responses and improves outcomes in Pax5−/+ mice susceptible to chronic infection

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity ( −/+ ), resulting in reduced PAX5 levels mice, mimics germline somatic dysregulation contributing diseases such as childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). In contrast the well-characterized roles of during early development, little known about how impacts We infected mice with noncytopathic Lymphocytic Choriomeningitis Virus (LCMV) and found infection chronic Docile strain resulted decreased survival mice. While adaptive CD8 + T-cell (CTL) immunity was robust LCMV-specific neutralizing antibody production compromised leading impaired long-term viral clearance pro-inflammatory milieu bone marrow (BM). Here we show outcomes were improved upon prophylactic treatment β-glucan trainer through induction heterologous protection against infection. β-Glucan enhanced clearance, CTL immunity, monocyte immunosuppression multiple LCMV-resident host organs. New insight from this study will help design effective strategies infections, particularly genetically predisposed susceptible hosts.

Language: Английский

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