Immunometabolism (Cobham (Surrey, England))最新文献

{"title":"Pathway thermodynamic analysis postulates change in glutamate metabolism as a key factor in modulating immune responses.","authors":"Sunayana Malla, Rajib Saha","doi":"10.1097/IN9.0000000000000077","DOIUrl":"10.1097/IN9.0000000000000077","url":null,"abstract":"<p><strong>Background: </strong>Temperature, as seen during fever, plays a pivotal role in modulating immune responses and maintaining cellular homeostasis. Shifts in temperature influence the thermodynamic feasibility of metabolic reactions, with Gibbs free energy (ΔG) serving as a key indicator of the spontaneity of reactions under specific conditions. By altering ΔG in response to temperature changes across various metabolite concentrations and cell types, we can gain insights into the thermodynamic properties of metabolic pathways and identify critical factors involved in metabolism and immune function. Using Max-min Driving Force (MDF) analysis, we can assess changes in ΔG by varying temperature and metabolite concentrations, allowing for a detailed examination of thermodynamic feasibility at both the pathway and individual reaction levels.</p><p><strong>Method: </strong>Minimum driving force analysis was conducted to estimate the thermodynamic feasibility of metabolic pathways, including glycolysis, gluconeogenesis, oxidative phosphorylation, the pentose phosphate pathway, the tricarboxylic acid cycle, arginine and proline metabolism, amino sugar and nucleotide sugar metabolism (collectively referred to as amino sugar metabolism), leukotriene metabolism, and other amino acid pathways. The analysis was performed across a temperature range of 310.15 to 314.15 K. In addition, the ΔG for each reaction was calculated using standard Gibbs free energy values obtained from the equilibrator.</p><p><strong>Results: </strong>In this study, MDF analysis is applied to measure the changes in the driving force of pathways and the ΔG of each reaction at normal human core temperature (310.15 K) and elevated temperatures (up to 314.15 K). Additionally, we explore how shifts in the thermodynamic feasibility of reactions under immune activation, compared with normal physiological conditions, highlight key metabolic intermediates, such as fructose-1,6-bisphosphate, glucose-6-phosphate, and several steps in glutamate utilization, as important regulators of metabolic processes and immune responses.</p><p><strong>Conclusion: </strong>In conclusion, this study demonstrates that MDF-based thermodynamic analysis effectively captures temperature-dependent shifts in metabolic pathway feasibility and highlights glutamate metabolism as a key regulator of immune function. These findings underscore the utility of thermodynamic frameworks in advancing system-level understanding of human metabolism and immune regulation.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"8 1","pages":"e00077"},"PeriodicalIF":3.9,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12940620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From lipid switch to tissue repair: how resolvins reprogram macrophage polarization and function.","authors":"Rebecca Buete, Jordan Scherer, Andreas Patsalos, Laszlo Nagy","doi":"10.1097/IN9.0000000000000076","DOIUrl":"10.1097/IN9.0000000000000076","url":null,"abstract":"<p><p>Specialized pro-resolving mediators (SPMs) derived from docosahexaenoic acid (DHA), particularly D-series resolvins (RvD1, RvD2, RvD3, and RvD5), function to terminate inflammation while preserving host defense. They are synthesized from DHA by lipoxygenases and act through G‑protein‑coupled receptors and lipid‑sensing transcription factors (TFs). These mediators reprogram macrophage metabolism towards fatty‑acid oxidation and oxidative phosphorylation, accelerate efferocytosis, and promote tissue repair. Here, we synthesize current knowledge on their biosynthesis, receptor signaling, and immunometabolic rewiring within macrophages, and critically appraise their therapeutic potential across cardiometabolic, musculoskeletal, autoimmune, and ischemia/reperfusion disorders. We also discuss analytical controversies surrounding their in vivo low‑abundance detection, and outline translational challenges including short half‑life, formulation stability, and emerging synthetic agonists. Finally, we propose priority research directions, from single-cell spatial lipidomics to clinical translation, to define the next frontier for resolvin-based immunotherapies.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"8 1","pages":"e00076"},"PeriodicalIF":3.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental origins of immunometabolic health.","authors":"Yem J Alharithi, Gladys Smith, Alina Maloyan","doi":"10.1097/IN9.0000000000000075","DOIUrl":"10.1097/IN9.0000000000000075","url":null,"abstract":"<p><p>Obesity during pregnancy not only affects maternal health but also puts offspring at high risk of obesity and of metabolic and cardiovascular diseases later in life, often regardless of their own lifestyle choices. This process, known as developmental programming, is increasingly being recognized as a critical factor shaping long-term health outcomes. In addition, a growing body of research highlights the importance of immunometabolism, the metabolism of immune cells, in the pathogenesis of obesity, metabolic disorders, cardiovascular disease, and cancer. Although the effects of maternal obesity on offspring health have been well documented in both epidemiological studies and preclinical models, its influence on the developing immune system and immunometabolic pathways is only beginning to be revealed. In this review, we explore the metabolic and inflammatory dimensions of developmental programming and discuss how an adverse maternal environment may shape the offspring's immunometabolic landscape.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"8 1","pages":"e00075"},"PeriodicalIF":3.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic deficits and immune dysfunction in aging people living with HIV.","authors":"Daniela Frasca, Suresh Pallikkuth","doi":"10.1097/IN9.0000000000000071","DOIUrl":"10.1097/IN9.0000000000000071","url":null,"abstract":"<p><p>Cellular metabolism is crucial for energy production, which regulates cell function and survival. In recent years, the importance of metabolism in modulating immune cell proliferation, differentiation, and function has become a prominent area of research. However, little is still known about the metabolic regulation of B cell function and humoral immunity, both in healthy individuals as well as in those with various conditions and diseases. In this viewpoint, we will discuss the current understanding of immunometabolic regulation of humoral responses in aging people living with HIV, and in people without HIV. We propose the possibility to target metabolic molecules and pathways to prevent the negative effects of aging and HIV and progress towards an overall better immune system, not only in individuals with HIV but also in those living with other inflammatory conditions and diseases.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"7 4","pages":"e00071"},"PeriodicalIF":2.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12622269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of immunometabolic profiles in whole blood versus peripheral blood mononuclear cells.","authors":"Ibrahima Diallo, Graham Heieis, Mikhael D Manurung, Marouba Cisse, Yoanne D Mouwenda, Yvonne C M Kruize, Moustapha Mbow, Maria Yazdanbakhsh, Bart Everts","doi":"10.1097/IN9.0000000000000073","DOIUrl":"10.1097/IN9.0000000000000073","url":null,"abstract":"<p><strong>Background: </strong>Immunometabolism has emerged as a flourishing field exploring how cellular metabolism regulates immune responses. Peripheral blood mononuclear cells (PBMCs) have so far been the primary sample type used for immunometabolic profiling. However, PBMCs isolation requires large blood volumes, can pose logistic challenges, and requires specialized skills for processing. Thus, using whole blood (WB) samples, which are less technically challenging to process, could serve as a viable alternative for metabolic characterization of circulating immune cell populations. Yet, how well WB immunometabolic profiles match those from PBMCs remains unknown. Therefore, we aimed to compare the immunometabolic profile of WB with that of PBMCs.</p><p><strong>Method: </strong>Paired WB and PBMCs samples were collected from six healthy donors. WB was collected in CryoStor^®-CS10 medium, while PBMCs were isolated using Ficoll density gradient. Using spectral flow cytometry, we identified immune cell populations and assessed their metabolic states.</p><p><strong>Results: </strong>Our findings show an overall high similarity in the immune cell subset frequencies between WB and PBMCs as well as their metabolic profiles. However, differences in the expression of certain metabolic markers were noted in some immune populations. Specifically, glucose transporter 1 levels were higher in CD8⁺ TEMRA, NKT, and NK cells from PBMCs, while ATP5a levels were higher in naïve CD4⁺ T cells from WB.</p><p><strong>Conclusions: </strong>These results suggest that WB can be an alternative to PBMCs for metabolic profiling of immune cells. Nevertheless, for some specific cell subsets, caution should be taken when comparing immunometabolic data between WB and PBMCs.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"7 4","pages":"e00073"},"PeriodicalIF":2.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12604536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of metaorganismal lipid metabolism in human health and disease.","authors":"William J Massey, Jonathan Mark Brown","doi":"10.1097/IN9.0000000000000074","DOIUrl":"10.1097/IN9.0000000000000074","url":null,"abstract":"<p><p>Most chronic diseases including coronary heart disease, obesity, diabetes, cancer, and multiple neurodegenerative diseases are driven by dysregulated lipid metabolism. In fact, many common drugs taken by millions including aspirin, statins, fibrates, and others improve health by reorganizing systemic lipid metabolism. Although we have a wealth of information on the enzymes and pathways maintaining lipid metabolic homeostasis in our human cells, there is much less known in regard to how our gut microbiome may coordinate with the host to control systemic lipid metabolism. With advances in untargeted metabolomics, there is a rapidly expanding list of gut microbe-derived lipid metabolites with unannotated function. Many of these bacterial lipids can be assimilated into host lipids and alter host lipid metabolic processes. Here, we discuss how gut microbe-derived lipids may be further metabolized by the host through metaorganismal metabolic pathways. We also discuss the untapped therapeutic potential for targeting metaorganismal lipid metabolism for the improvement of human health.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"7 4","pages":"e00074"},"PeriodicalIF":3.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12594153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A carbon trail to follow: unveiling itaconate's metabolism in vivo.","authors":"Denis E Anisov, Sally A Clayton, Maxim A Nosenko","doi":"10.1097/IN9.0000000000000072","DOIUrl":"10.1097/IN9.0000000000000072","url":null,"abstract":"<p><p>The discovery of itaconate as an immunoregulatory metabolite has transformed the field of immunometabolism and opened multiple therapeutic avenues over the past decade. While the immunological functions of itaconic acid have been extensively studied, several aspects of its biochemistry-particularly in vivo utilization pathways-have remained unclear. In a recent study published in <i>Nature Metabolism</i>, Willenbockel et al apply carbon tracing to uncover the metabolic fate of itaconate within the organism. Insights from this work have important implications for understanding the physiological roles of itaconate and for advancing itaconate-based therapeutic strategies.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"7 4","pages":"e00072"},"PeriodicalIF":2.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12558001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145395488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunometabolism at the crossroads of infection: mechanistic and systems-level perspectives from host and pathogen.","authors":"Sunayana Malla, Nabia Shahreen, Rajib Saha","doi":"10.1097/IN9.0000000000000069","DOIUrl":"10.1097/IN9.0000000000000069","url":null,"abstract":"<p><p>The emerging field of immunometabolism has underscored the central role of metabolic pathways in orchestrating immune cell function. Far from being passive background processes, metabolic activities actively regulate key immune responses. Fundamental pathways such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation critically shape the behavior of immune cells, influencing macrophage polarization, T cell activation, and dendritic cell function. In this review, we synthesize recent advances in immunometabolism, with a focus on the metabolic mechanisms that govern the responses of both innate and adaptive immune cells to bacterial, viral, and fungal pathogens. Drawing on experimental, computational, and integrative methodologies, we highlight how metabolic reprogramming contributes to host defense in response to infection. These findings reveal new opportunities for therapeutic intervention, suggesting that modulation of metabolic pathways could enhance immune function and improve pathogen clearance.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"7 4","pages":"e00069"},"PeriodicalIF":2.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12558011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145395519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTRP6 as a negative regulator of anti-inflammatory M2 macrophage polarization.","authors":"Jeevotham Senthil Kumar, Emma Kempton, Muhammad Zubair Mehboob, Dingbo Lin, Xia Lei","doi":"10.1097/IN9.0000000000000070","DOIUrl":"10.1097/IN9.0000000000000070","url":null,"abstract":"<p><strong>Background: </strong>Chronic low-grade inflammation in adipose tissue, primarily driven by macrophages, plays a central role in obesity pathophysiology. C1q/TNF-related protein 6 (CTRP6), a member of the CTRP family, has emerged as a key regulator of this inflammatory process. Here, we demonstrate that CTRP6 expression is upregulated in adipose tissue macrophages during obesity, where it acts as a potent modulator of macrophage polarization by suppressing M2 polarization.</p><p><strong>Methods: </strong>In RAW264.7 macrophages, we distinguished M1 and M2 polarization, induced by lipopolysaccharide (LPS) + interferon-gamma (IFNγ) and interleukin (IL)-4, respectively, by selecting two marker genes for each polarization type from a set of five widely used markers, based on a time-course analysis. We then assessed the effects of recombinant CTRP6 protein treatment on M1 and M2 polarization. Finally, we validated our findings in primary bone marrow-derived macrophages (BMDMs).</p><p><strong>Results: </strong>In naïve RAW264.7 macrophages, recombinant CTRP6 protein upregulated M1 marker genes (<i>Tnf</i>, <i>Nos2</i>) while downregulating M2 markers (<i>Mrc1</i>, <i>Pparg</i>). During M1 polarization induced by LPS+IFNγ, CTRP6 treatment had no significant effect. However, during IL-4-induced M2 polarization, CTRP6 not only enhanced M1 markers but also strongly suppressed M2 markers by inhibiting anti-inflammatory signal transducer and activator of transcription 6 (STAT6) signaling and relieving the inhibition of pro-inflammatory ERK1/2 signaling. Additionally, CTRP6 impaired mitochondrial activity, favoring glycolysis in macrophages. Importantly, these effects were serum-independent and confirmed in BMDMs.</p><p><strong>Conclusions: </strong>Since endogenous CTRP6 expression in BMDMs is upregulated by M1 polarization inducers, it may further hinder inflammation resolution, even in the presence of IL-4 during tissue repair, establishing it as a key driver of adipose tissue inflammation in obesity.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"7 4","pages":"e00070"},"PeriodicalIF":2.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12558006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145395523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID.","authors":"Yijuan Zhu, Patrick Quan, Tadahiro Yamazaki, Anna Norweg, Benjamin Natelson, Xiang Xu","doi":"10.1097/IN9.0000000000000068","DOIUrl":"10.1097/IN9.0000000000000068","url":null,"abstract":"<p><p>Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID are complex, disabling conditions that have emerged as significant public health challenges, affecting millions worldwide. Despite their growing prevalence, effective diagnostics and treatments remain limited, largely due to an incomplete understanding of their underlying pathophysiology. Both conditions share hallmark symptoms of chronic fatigue, cognitive dysfunction, and postexertional malaise, but their biological underpinnings remain to be elucidated. Neuroimaging offers a promising, noninvasive window into the brain's metabolic landscape and has the potential to uncover objective biomarkers for these conditions. In this mini review, we highlight recent advancements in metabolic neuroimaging, particularly positron emission tomography and magnetic resonance imaging/magnetic resonance spectroscopy, that reveal alterations in glucose and oxygen metabolism, neurotransmitter balance, and oxidative stress. These insights point toward shared disruptions in brain energy metabolism and neuroinflammatory processes, which may underlie the persistent symptoms in both ME/CFS and Long-COVID. Importantly, while some findings overlap, inconsistencies in metabolite profiles between ME/CFS and Long-COVID underscore the need for further stratification and longitudinal research. Standardizing definitions, such as identifying Long-COVID patients who meet ME/CFS diagnostic criteria, could help improve study comparability. By summarizing current imaging evidence, this review underscores the potential of neuroimaging to identify imaging biomarkers to advance the clinical diagnosis of Long-COVID and identify therapeutic targets for treatment development. As we continue to face the growing burden of Long-COVID and ME/CFS, metabolic imaging may serve as a powerful tool to bridge gaps in knowledge and accelerate progress toward effective care.</p>","PeriodicalId":73349,"journal":{"name":"Immunometabolism (Cobham (Surrey, England))","volume":"7 4","pages":"e00068"},"PeriodicalIF":3.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}