Apoptotic cells secrete metabolites to regulate immune homeostasis

Baxter, Amy A.; Poon, Ivan K. H.

doi:10.1111/imcb.12333

Cited by 4 publications

(3 citation statements)

References 24 publications

(28 reference statements)

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“…It has been described that the biochemical features distinctive of COVID-19 sepsis point to a state of acute inflammation with a cytokine storm associated with an altered metabolism [ 47 ] that modulates immune responses against infectious agents, increasing or decreasing the release of pro- and anti-inflammatory cytokines [ 48 ]. During this process, activated immune cells undergo extensive metabolic rewiring for energy and biomass generation whereby metabolites become important regulators of immunity and disease [ 49 ]. However, in the context of the COVID-19 pandemic, there is limited data exploring the interplay between metabolism and immune system [ 50 – 54 ].…”

Section: Discussionmentioning

confidence: 99%

Immunometabolic signatures predict risk of progression to sepsis in COVID-19

et al. 2021

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Viral sepsis has been proposed as an accurate term to describe all multisystemic dysregulations and clinical findings in severe and critically ill COVID-19 patients. The adoption of this term may help the implementation of more accurate strategies of early diagnosis, prognosis, and in-hospital treatment. We accurately quantified 110 metabolites using targeted metabolomics, and 13 cytokines/chemokines in plasma samples of 121 COVID-19 patients with different levels of severity, and 37 non-COVID-19 individuals. Analyses revealed an integrated host-dependent dysregulation of inflammatory cytokines, neutrophil activation chemokines, glycolysis, mitochondrial metabolism, amino acid metabolism, polyamine synthesis, and lipid metabolism typical of sepsis processes distinctive of a mild disease. Dysregulated metabolites and cytokines/chemokines showed differential correlation patterns in mild and critically ill patients, indicating a crosstalk between metabolism and hyperinflammation. Using multivariate analysis, powerful models for diagnosis and prognosis of COVID-19 induced sepsis were generated, as well as for mortality prediction among septic patients. A metabolite panel made of kynurenine/tryptophan ratio, IL-6, LysoPC a C18:2, and phenylalanine discriminated non-COVID-19 from sepsis patients with an area under the curve (AUC (95%CI)) of 0.991 (0.986–0.995), with sensitivity of 0.978 (0.963–0.992) and specificity of 0.920 (0.890–0.949). The panel that included C10:2, IL-6, NLR, and C5 discriminated mild patients from sepsis patients with an AUC (95%CI) of 0.965 (0.952–0.977), with sensitivity of 0.993(0.984–1.000) and specificity of 0.851 (0.815–0.887). The panel with citric acid, LysoPC a C28:1, neutrophil-lymphocyte ratio (NLR) and kynurenine/tryptophan ratio discriminated severe patients from sepsis patients with an AUC (95%CI) of 0.829 (0.800–0.858), with sensitivity of 0.738 (0.695–0.781) and specificity of 0.781 (0.735–0.827). Septic patients who survived were different from those that did not survive with a model consisting of hippuric acid, along with the presence of Type II diabetes, with an AUC (95%CI) of 0.831 (0.788–0.874), with sensitivity of 0.765 (0.697–0.832) and specificity of 0.817 (0.770–0.865).

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Section: Discussionmentioning

confidence: 99%

Immunometabolic signatures predict risk of progression to sepsis in COVID-19

et al. 2021

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“…Thus, Mφ-apoEVs and OC-apoEVs may also be taken up by local MSCs and enhance the proliferation and chondrogenic/osteogenic differentiation of MSCs. In addition to cell surface determinants, recent studies have shown that the apoptotic metabolite secretum induces specific gene programs in neighboring cells [ 38 , 39 ], indicating that the cargo within apoptotic cells and EVs is also important. This may explain the different effects of Mφ-apoEVs and OC-apoEVs on osteogenesis and bone formation.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic extracellular vesicles restore homeostasis of the articular microenvironment for the treatment of rheumatoid arthritis

Li,

et al. 2024

Bioactive Materials

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“…We postulate that signaling via apoptotic metabolites induces threshold-specific transcription programs similar to QS. Elevated apoptotic metabolite concentrations can conceivably modulate synergistic macrophage responses in dynamic tissue parameters such as collateral tissue damage and infectious disease [ 143 ]. Moreover, metabolites that are secreted or diffuse from apoptotic cells, such as ATP and ADP, can regulate both the adaptive and innate immune system simultaneously to coordinate the immune response and immune cell homeostasis [ 144 , 145 , 146 , 147 , 148 ], thus endowing it with a QS-like mechanism to regulate tissue populations in response to local cell death ( Figure 3 ).…”

Section: Qs-like Regulation Of Myeloid Cells and The Innate Immune Sy...mentioning

confidence: 99%

Immunoregulation via Cell Density and Quorum Sensing-like Mechanisms: An Underexplored Emerging Field with Potential Translational Implications

Naoun

Raphael

Forsthuber

2022

Cells

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Quorum sensing (QS) was historically described as a mechanism by which bacteria detect and optimize their population density via gene regulation based on dynamic environmental cues. Recently, it was proposed that QS or similar mechanisms may have broader applications across different species and cell types. Indeed, emerging evidence shows that the mammalian immune system can also elicit coordinated responses on a population level to regulate cell density and function, thus suggesting that QS-like mechanisms may also be a beneficial trait of the immune system. In this review, we explore and discuss potential QS-like mechanisms deployed by the immune system to coordinate cellular-level responses, such as T cell responses mediated via the common gamma chain (γc) receptor cytokines and the aryl hydrocarbon receptors (AhRs). We present evidence regarding a novel role of QS as a multifunctional mechanism coordinating CD4+ and CD8+ T cell behavior during steady state and in response to infection, inflammatory diseases, and cancer. Successful clinical therapies such as adoptive cell transfer for cancer treatment may be re-evaluated to harness the effects of the QS mechanism(s) and enhance treatment responsiveness. Moreover, we discuss how signaling threshold perturbations through QS-like mediators may result in disturbances of the complex crosstalk between immune cell populations, undesired T cell responses, and induction of autoimmune pathology. Finally, we discuss the potential therapeutic role of modulating immune-system-related QS as a promising avenue to treat human diseases.

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Apoptotic cells secrete metabolites to regulate immune homeostasis

Cited by 4 publications

References 24 publications

Immunometabolic signatures predict risk of progression to sepsis in COVID-19

Immunometabolic signatures predict risk of progression to sepsis in COVID-19

Apoptotic extracellular vesicles restore homeostasis of the articular microenvironment for the treatment of rheumatoid arthritis

Immunoregulation via Cell Density and Quorum Sensing-like Mechanisms: An Underexplored Emerging Field with Potential Translational Implications

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