Immunopathophysiology of human sepsis

EBioMedicine, Journal Year: 2022, Volume and Issue: 86, P. 104363 - 104363

Published: Dec. 1, 2022

Language: Английский

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The pathophysiology of sepsis and precision-medicine-based immunotherapy

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(1), P. 19 - 28

Published: Jan. 1, 2024

Language: Английский

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Antibiotic failure: Beyond antimicrobial resistance

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101012 - 101012

Published: Oct. 18, 2023

Language: Английский

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Immune dysregulation in sepsis: experiences, lessons and perspectives

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Dec. 19, 2023

Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host responses to infection. Not only does sepsis pose serious hazard human health, but it also imposes substantial economic burden on the healthcare system. The cornerstones of current treatment for remain source control, fluid resuscitation, and rapid administration antibiotics, etc. To date, no drugs have been approved treating sepsis, most clinical trials potential therapies failed reduce mortality. immune response pathogen complex, resulting in innate adaptive that, if not promptly controlled, can lead excessive inflammation, immunosuppression, failure re-establish homeostasis. impaired patients with immunotherapy modulate causing inflammation or enhancing immunity suggest importance demonstrating individualized therapy. Here, we review where cell production, effector function, survival are directly affected during sepsis. In addition, discuss septic highlight need precise according stratification.

Language: Английский

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Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 13, 2023

Abstract Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as capacity preserve and/or rapidly restore functions that promote disease resistance (immunocompetence) and control inflammation infectious diseases well other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics quantify balance between (i) CD8 + CD4 T-cell (ii) gene expression signatures tracking longevity-associated immunocompetence mortality-associated inflammation. Profiles ~48,500 individuals collectively indicate some persons resist degradation both during aging when challenged varied stressors. With resistance, preservation tracked a lower risk HIV acquisition, AIDS development, symptomatic influenza infection, recurrent skin cancer; survival COVID-19 sepsis; (iii) longevity. potentially reversible by decreasing Overall, show trait observed across age spectrum, more common females, aligned specific immunocompetence-inflammation linked favorable immunity-dependent health outcomes. mechanisms have utility biomarkers for measuring improving

Language: Английский

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Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 12(4), P. 305 - 322

Published: Dec. 21, 2023

Language: Английский

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Surviving Sepsis Campaign Research Priorities 2023

Critical Care Medicine, Journal Year: 2024, Volume and Issue: 52(2), P. 268 - 296

Published: Jan. 19, 2024

OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis septic shock. DESIGN: Shortly after publication most recent Surviving Sepsis Campaign Guidelines, Research Committee, a multiprofessional group 16 international experts representing European Society Intensive Care Medicine Critical Medicine, convened virtually iteratively developed article recommendations, which represents an update from 2018 Priorities. METHODS: Each task force member submitted five questions on any sepsis-related subject. Committee members then independently ranked their top three list generated. The highest rated clinical basic science were into current article. RESULTS: A total 81 submitted. After merging similar questions, there 34 ten for voting. as follows: 1) what is best strategy screening identification patients with sepsis, can predictive modeling assist real-time recognition sepsis? 2) causes organ injury dysfunction how should it be defined, detected? 3) fluid resuscitation individualized initially beyond? 4) vasopressor approach treating different phases shock? 5) personalized/precision medicine optimal therapies to improve patient outcomes? How we animal models so that they more closely resemble humans? What outcome variables maximize correlations between human are therefore appropriate use both? does affect brain, do sepsis-induced brain alterations contribute dysfunction? interactions neural, endocrine, immune systems? microbiome pathobiology? genetics epigenetics influence development course response treatments CONCLUSIONS: Knowledge advances multiple domains have been incorporated progressive iterations guidelines, allowing evidence-based recommendations short- long-term management sepsis. However, strength existing evidence modest significant knowledge gaps mortality remains high. identified represent roadmap

Language: Английский

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Advances and Challenges in Sepsis Management: Modern Tools and Future Directions

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 439 - 439

Published: March 2, 2024

Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte subsets, leading to diminished effector functions, altered cytokine profiles, metabolic changes. The complexity of sepsis stems not only from its pathophysiology also the heterogeneity patient responses, posing significant challenges developing universally effective therapies. review emphasizes importance phenotyping enhance patient-specific diagnostic therapeutic strategies. Phenotyping cells, which categorizes patients based on clinical immunological characteristics, is pivotal for tailoring treatment approaches. Flow cytometry emerges as crucial tool this endeavor, offering rapid, low cost detailed analysis cell populations their functional states. Indeed, technology facilitates understanding dysfunctions contributes identification novel biomarkers. Our underscores potential integrating flow with omics data, machine learning observations refine management, highlighting shift towards personalized medicine care. approach could lead more precise interventions, improving outcomes heterogeneously affected population.

Language: Английский

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Nonenzymatic lysine d-lactylation induced by glyoxalase II substrate SLG dampens inflammatory immune responses

Cell Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Abstract Immunometabolism is critical in the regulation of immunity and inflammation; however, mechanism preventing aberrant activation-induced immunopathology remains largely unclear. Here, we report that glyoxalase II (GLO2) glycolysis branching pathway specifically downregulated by NF-κB signaling during innate immune activation via tristetraprolin (TTP)-mediated mRNA decay. As a result, its substrate S -D-lactoylglutathione (SLG) accumulates cytosol directly induces d -lactyllysine modification proteins. This nonenzymatic lactylation SLG greatly facilitated nearby cysteine residue, as it initially reacts with to form reversible -lactylated thiol intermediate, followed SN -transfer lactyl moiety proximal lysine. Lactylome profiling identifies 2255 sites mostly cytosolic proteins activated macrophages, global protein structure analysis suggests proximity residue determines susceptibility lysine SLG-mediated -lactylation. Furthermore, preferentially enriched involved inflammatory pathways, -lactylation at 310 (K310) RelA attenuates transcriptional activity restore homeostasis. Accordingly, TTP-binding site mutation or overexpression GLO2 vivo blocks this feedback cells promotes inflammation, whereas genetic deficiency pharmacological inhibition restricts both vitro vivo. Importantly, dysregulation GLO2/SLG/ regulatory axis closely associated human phenotypes. Overall, our findings uncover an immunometabolic loop SLG-induced implicate promising target for combating clinical disorders.

Language: Английский

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Harnessing artificial intelligence in sepsis care: advances in early detection, personalized treatment, and real-time monitoring

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 6, 2025

Sepsis remains a leading cause of morbidity and mortality worldwide due to its rapid progression heterogeneous nature. This review explores the potential Artificial Intelligence (AI) transform sepsis management, from early detection personalized treatment real-time monitoring. AI, particularly through machine learning (ML) techniques such as random forest models deep algorithms, has shown promise in analyzing electronic health record (EHR) data identify patterns that enable detection. For instance, have demonstrated high accuracy predicting onset intensive care unit (ICU) patients, while approaches been applied recognize complications sepsis-associated acute respiratory distress syndrome (ARDS). Personalized plans developed AI algorithms predict patient-specific responses therapies, optimizing therapeutic efficacy minimizing adverse effects. AI-driven continuous monitoring systems, including wearable devices, provide predictions sepsis-related complications, enabling timely interventions. Beyond these advancements, enhances diagnostic accuracy, predicts long-term outcomes, supports dynamic risk assessment clinical settings. However, ethical challenges, privacy concerns algorithmic biases, must be addressed ensure fair effective implementation. The significance this lies addressing current limitations management highlighting how can overcome hurdles. By leveraging healthcare providers significantly enhance optimize protocols, improve overall patient outcomes. Future research should focus on refining with diverse datasets, integrating emerging technologies, fostering interdisciplinary collaboration address challenges realize AI's transformative care.

Language: Английский

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