Trained immunity: General and emerging concepts

Immunological Reviews, Год журнала: 2024, Номер 323(1), С. 164 - 185

Опубликована: Март 29, 2024

Summary Over the past decade, compelling evidence has unveiled previously overlooked adaptive characteristics of innate immune cells. Beyond their traditional role in providing short, non‐specific protection against pathogens, cells can acquire antigen‐agnostic memory, exhibiting increased responsiveness to secondary stimulation. This long‐term de‐facto also termed trained immunity , is mediated through extensive metabolic rewiring and epigenetic modifications. While upregulation proves advantageous countering paralysis, its overactivation contributes pathogenesis autoinflammatory autoimmune disorders. In this review, we present latest advancements field memory followed by a description fundamental mechanisms underpinning generation different cell types that mediate it. Furthermore, explore implications for various diseases examine current limitations potential therapeutic targeting immune‐related

Язык: Английский

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MMR vaccination induces trained immunity via functional and metabolic reprogramming of γδ T cells

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(7)

Опубликована: Янв. 30, 2024

The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In randomized placebo-controlled trial, 39 healthy adults received either or placebo. By using single-cell RNA-sequencing, we found caused transcriptomic CD14-positive monocytes NK most profoundly γδ T cells. Monocyte function was not altered by vaccination. contrast, of cells markedly enhanced vaccination, with higher production TNF IFNγ, as well upregulation cellular metabolic pathways. conclusion, describe immunity program characterized modulation cell induced

Язык: Английский

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The chromatin landscape of healthy and injured cell types in the human kidney

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 10, 2024

There is a need to define regions of gene activation or repression that control human kidney cells in states health, injury, and repair understand the molecular pathogenesis disease design therapeutic strategies. Comprehensive integration expression with epigenetic features regulatory elements remains significant challenge. We measure dual single nucleus RNA chromatin accessibility, DNA methylation, H3K27ac, H3K4me1, H3K4me3, H3K27me3 histone modifications decipher landscape regulation reference adaptive injury states. establish spatially-anchored epigenomic atlas kidney's active, silent, accessible across genome. Using this atlas, we note distinct different epithelial cell types. A proximal tubule transcription factor network ELF3, KLF6, KLF10 regulates transition between health while thick ascending limb regulated by NR2F1. Further, combined perturbation distinguishes two tubular subtypes, one which manifested trajectory after knockout. This will serve as foundation facilitate targeted cell-specific therapeutics reprogramming networks.

Язык: Английский

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Vaccine adjuvants: Tailoring innate recognition to send the right message

Immunity, Год журнала: 2024, Номер 57(4), С. 772 - 789

Опубликована: Апрель 1, 2024

Язык: Английский

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The interaction of innate immune and adaptive immune system

MedComm, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 15, 2024

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific sustained killing via B cells, T antibodies. Traditionally, it has been assumed that activates immunity; however, recent studies have revealed more complex interactions. This review a detailed dissection composition function systems, emphasizing their synergistic roles in physiological pathological contexts, providing new insights into link between these two forms immunity. Precise regulation both systems at same time is beneficial fight against immune-related diseases, for example, cGAS-STING pathway found play an important role infections cancers. In addition, paper summarizes challenges future directions field immunity, including latest single-cell sequencing technologies, CAR-T cell therapy, checkpoint inhibitors. By summarizing developments, aims enhance our understanding complexity interactions perspectives system.

Язык: Английский

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Mechanisms and Clinical Implications of Human Gut Microbiota-Drug Interactions in the Precision Medicine Era

Biomedicines, Год журнала: 2024, Номер 12(1), С. 194 - 194

Опубликована: Янв. 16, 2024

The human gut microbiota, comprising trillions of microorganisms residing in the gastrointestinal tract, has emerged as a pivotal player modulating various aspects health and disease. Recent research shed light on intricate relationship between microbiota pharmaceuticals, uncovering profound implications for drug metabolism, efficacy, safety. This review depicted landscape molecular mechanisms clinical dynamic Microbiota-Drug Interactions (MDI), with an emphasis impact MDI responses individual variations. also discussed therapeutic potential or harnessing its metabolic capabilities to optimize treatments advance personalized medicine, well challenges future directions this emerging field.

Язык: Английский

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Transforming vaccinology

Cell, Год журнала: 2024, Номер 187(19), С. 5171 - 5194

Опубликована: Сен. 1, 2024

Язык: Английский

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Trained immunity in chronic inflammatory diseases and cancer

Nature reviews. Immunology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Язык: Английский

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Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection

Science Translational Medicine, Год журнала: 2025, Номер 17(783)

Опубликована: Янв. 29, 2025

At this stage in the COVID-19 pandemic, most infections are "breakthrough" that occur individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity breakthrough infections. We performed single-cell transcriptomic, proteomic, functional profiling of primary to compare immune responses from unvaccinated vaccinated during SARS-CoV-2 Delta wave. Breakthrough were characterized by a less activated transcriptomic profile monocytes natural killer cells, induction pathways limiting monocyte migratory potential cell proliferation. Furthermore, observed female-specific increase proteomic activation multiple subsets These insights suggest vaccination prevents overactivation discernible sex-specific patterns underscore harnessing vaccines mitigating pathologic resulting overactivation.

Язык: Английский

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Linking vaccine adjuvant mechanisms of action to function

Science Immunology, Год журнала: 2025, Номер 10(104)

Опубликована: Фев. 14, 2025

Vaccines deliver an immunogen in a manner designed to safely provoke immune response, leading the generation of memory T and B cells long-lived antibody-producing plasma cells. Adjuvants play critical role vaccines by controlling how system is exposed providing inflammatory cues that enable productive priming. However, mechanisms action underlying adjuvant function at molecular, cell, tissue levels are diverse often poorly understood. Here, we review current understanding adjuvants used subunit protein/polysaccharide mRNA vaccines, discuss where possible these link downstream effects on identify knowledge gaps will be important fill order continued development more effective for challenging pathogens such as HIV emerging threats.

Язык: Английский

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