From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis

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

Published: Aug. 26, 2024

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents pivotal factor global mortality attributed diseases. The recent consensus delineates sepsis as perilous state of organ dysfunction arising from the host’s maladaptive reaction infection. It masks complexity breadth mechanisms involved sepsis, which characterized simultaneous hyperinflammation immunosuppression. highly correlated with response, mainly mediated various cells their interactions. This can lead plethora complications, encompassing systemic inflammatory metabolic disturbances, infectious shock, MODS, DIC. Furthermore, more research studies have been conducted on past few years. pathological characteristics improved or treated targeting signaling pathways like NF-B, JAK–STAT, PI3K-Akt, p38-MAPK. Combined drug therapy better than single for sepsis. article will review latest progress pathogenesis treatment

Language: Английский

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Deficient neutrophil responses early in influenza infection promote viral replication and pulmonary inflammation

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012449 - e1012449

Published: Jan. 17, 2025

Neutrophils play key protective roles in influenza infections, yet excessive neutrophilic inflammation is a hallmark of acute lung injury during severe infections. Phenotypic heterogeneity increasingly recognized neutrophil populations; however, how functional variation neutrophils between individuals determine the diverse outcomes remains unclear. To examine immunologic responses that may drive varying influenza, we infected C57BL/6 (B6) and A/J mice with mouse-adapted A virus A/PR/8/34 H1N1. self-resolving dose B6 was lethal mice, which had increased viral load throughout infection accompanied by prominent bronchoalveolar neutrophilia pulmonary vascular leakage preceding mortality. Notably, heavily recruited to lungs early while failed do so. from additionally displayed reduced extracellular trap (NET) release reactive oxygen species (ROS) generation compared infection, suggesting failure control product deficient response. if strains governed inflammation, adoptively transferred bone marrow or donors recipients found transfer enhanced clearance abrogated dissemination CXCL1 IL-6. The neutrophils, achieve either. Furthermore, were capable greater levels killing vitro than their counterparts. These results suggest moderator infection. Thus, host-specific differences both recruitment these cells as well interindividual ability support part dictate differing susceptibility respiratory

Language: Английский

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P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury

Clinical Immunology, Journal Year: 2024, Volume and Issue: 263, P. 110206 - 110206

Published: April 8, 2024

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found significant elevation CD64

Language: Английский

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The dual role of neutrophils in sepsis-associated liver injury

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Sepsis is often accompanied by liver injury and associated with an increase in the number of circulating hepatic neutrophils. In sepsis-associated injury, neutrophils exhibit phenotypic heterogeneity perform both pro- anti-inflammatory functions. Moreover, neutrophil dysfunction neutrophil-associated immunosuppression are also involved pathogenesis sepsis. Given complex functionality this cell type, aim review was to describe possible mechanistic role a brief introduction recruitment subsequent discussion potential contributions different subtypes injury.

Language: Английский

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Identifying early predictive and diagnostic biomarkers and exploring metabolic pathways for sepsis after trauma based on an untargeted metabolomics approach

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 8, 2025

Abstract Systemic inflammatory response syndrome (SIRS) and organ dysfunction make it challenging to predict which major trauma patients are at risk of developing sepsis. Additionally, the unclear pathogenesis sepsis after contributes its high morbidity mortality. Identifying early predictive diagnostic biomarkers, as well exploring related metabolic pathways, is crucial for improving prevention, diagnosis, treatment. This study prospectively analyzed plasma samples from with severe collected between March 2022 November 2023. Trauma were divided into two groups based on whether they developed within weeks: TDDS group (trauma who did not develop sepsis) TDS sepsis). Plasma time diagnosis (Sepsis group). Metabolite concentrations measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) through untargeted metabolomics. From differential metabolites groups, we identified five significant (all area under curve (AUC) ≥ 0.94) biomarkers trauma: (1) docosatrienoic acid, (2) 7-alpha-carboxy-17-alpha-carboxyethylandrostan lactone phenyl ester, (3) sphingomyelin (SM) 8:1;2O/26:1, (4) N1-[1-(3-isopropenylphenyl)-1-methylethyl]-3-oxobutanamide, (5) SM 34:2;2O. Furthermore, AUC 0.85) comparison groups: lysophosphatidylcholine (LPC) O-22:1, LPC O-22:0, uric O-24:2, 22:0-SN1. 26 shared comparisons (TDS vs. TDS) identified. Of which, 19 belong lipid metabolism. The top three pathways impact were: glycerophospholipid metabolism, porphyrin sphingolipid infection caffeine biosynthesis unsaturated fatty acids, steroid hormone biosynthesis. Our explored trauma. These findings provide a foundation future research onset development sepsis, facilitating treatment specific pathways.

Language: Английский

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Platelet Metabolites as Candidate Biomarkers in Sepsis Diagnosis and Management Using the Proposed Explainable Artificial Intelligence Approach

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(17), P. 5002 - 5002

Published: Aug. 23, 2024

: Sepsis is characterized by an atypical immune response to infection and a dangerous health problem leading significant mortality. Current diagnostic methods exhibit insufficient sensitivity specificity require the discovery of precise biomarkers for early diagnosis treatment sepsis. Platelets, known their hemostatic abilities, also play important role in immunological responses. This study aims develop model integrating machine learning explainable artificial intelligence (XAI) identify novel platelet metabolomics markers

Language: Английский

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Evaluation of the innate immune response of caprine neutrophils against Mycobacterium avium subspecies paratuberculosis in vitro

Veterinary Research, Journal Year: 2023, Volume and Issue: 54(1)

Published: July 18, 2023

Neutrophils constitute an essential component of the innate immune response, readily killing most bacteria through phagocytosis, degranulation, and release neutrophil extracellular traps (NETs) among other mechanisms. These cells play unclear role in mycobacterial infections such as Mycobacterium avium subspecies paratuberculosis (Map), etiological agent paratuberculosis, its response is particularly understudied ruminants. Herein, a wide set techniques were adapted, or newly developed, to study vitro caprine neutrophils after Map infection. Immunofluorescence was used demonstrate, simultaneously, chemotaxis, NETs. The quantification phagocytic activity against at 1:10 multiplicity infection (MOI), flow cytometry, showed values that varied from 4.54 5.63% phagocyting neutrophils. By immunofluorescence, 73.3 ± 14.5% fields NETs, mean DNA, attributable NETosis, calculated fluorometric method, 16.2 3.5%. In addition, RNA expression TGF-β, TNF IL-1β cytokines, measured reverse transcription qPCR, significantly higher two latter. Overall, proportional number bacteria. This work confirms simultaneous several mechanisms, combination different methodologies, are reach comprehensive understanding pathogens, demonstrates that, vitro, display strong Map, using their entire repertoire effector functions, sets basis for further vivo studies on paratuberculosis.

Language: Английский

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Protocol for density gradient neutrophil isolation and flow cytometry-based characterization from human peripheral blood

STAR Protocols, Journal Year: 2023, Volume and Issue: 4(3), P. 102497 - 102497

Published: Aug. 16, 2023

Neutrophils are the first immune responders to bacterial or viral infection and play key roles in host response; however, handling investigating fresh neutrophils can be challenging. Here, we present a protocol for isolating from peripheral blood of healthy donors using density gradient separation method. We describe steps morphology analysis by cytospin immunophenotyping flow cytometry analysis. This used isolation diseased individuals. For complete details on use execution this protocol, please refer Parthasarathy et al.

Language: Английский

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Clinical and Immunologic Correlates of Vasodilatory Shock Among Ebola Virus–Infected Nonhuman Primates in a Critical Care Model

The Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 228(Supplement_7), P. S635 - S647

Published: Aug. 30, 2023

Abstract Background Existing models of Ebola virus infection have not fully characterized the pathophysiology shock in connection with daily virologic, clinical, and immunologic parameters. We implemented a nonhuman primate critical care model to investigate these associations. Methods Two rhesus macaques received target dose 1000 plaque-forming units intramuscularly supportive initiated on day 3. High-dimensional spectral cytometry was used phenotype neutrophils peripheral blood mononuclear cells daily. Results observed progressive vasodilatory preserved cardiac function following viremia onset 5. Multiorgan dysfunction began 6 coincident nadir circulating neutrophils. Consumptive coagulopathy anemia occurred days 7 8 along irreversible shock, followed by death. The monocyte repertoire shifting 4 decline classical expansion double-negative monocytes. A selective loss CXCR3-positive B T cells, naive activation natural killer onset. Conclusions Our allows for high-fidelity characterization acute host innate adaptive immune responses, which may advance host-targeted therapy design evaluation use after multiorgan failure.

Language: Английский

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OMIP‐100: A flow cytometry panel to investigate human neutrophil subsets

Cytometry Part A, Journal Year: 2024, Volume and Issue: 105(2), P. 81 - 87

Published: Jan. 5, 2024

This 14-color, 13-antibody optimized multicolor immunofluorescence panel (OMIP) was designed for deep profiling of neutrophil subsets in various types human samples to contextualize plasticity a range healthy and diseased states. Markers present the OMIP allow associated with ontogeny, migration, phagocytosis capacity, granule release, immune modulation. For design, we ensured that commonly available fluorophores FITC/AF488, PE, APC were assigned intracellular subset marker Olfactomedin 4, maturity activation CD10, whole blood CD177, respectively. These markers can be easily replaced without affecting core identification neutrophils, enabling antibodies new antigens interest or fluorescent substrates assess different functions explored. Panel optimization performed on purified neutrophils. We demonstrate applications clinical (whole saliva) experimental endpoints (purified neutrophils stimulated through an vitro transmigration assay). hope providing uniform platform analyze sample will facilitate future understanding health disease.

Language: Английский

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