Immunometabolism: new insights and lessons from antigen-directed cellular immune responses

Ramalho, Renata; Rao, Martin; Zhang, C; Agrati, Chiara; Ippolito, Giuseppe; Wang, Fu Sheng; Zumla, Alimuddin; Maeurer, Markus

doi:10.1007/s00281-020-00798-w

Cited by 48 publications

(40 citation statements)

References 408 publications

(464 reference statements)

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“…Metabolites not only provide energy and substrates for cell growth and survival [ 64 ] but also regulate the function of immune cells [ 65 , 66 ]. The immune response and metabolism regulation are highly integrated and interdependent [ 67 ].…”

Section: Proteomic/metabolomic Features Associated With Severe Covid-19mentioning

confidence: 99%

“…In addition, T cell apoptosis in severe COVID-19 is inhibited in vitro by targeting voltage-dependent anion channel 1 oligomerization, which is associated with mitochondrial dysfunction and apoptosis [ 68 ]. Thus, evidence emerges that targeting specific metabolic events can strengthen antiviral immune responses while limiting nonproductive and adverse inflammation [ 66 ].…”

Section: Proteomic/metabolomic Features Associated With Severe Covid-19mentioning

confidence: 99%

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Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

Wang

Liu

et al. 2021

Cell Mol Immunol

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In response to emerging infectious diseases, such as the recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to quickly identify and understand responsible pathogens, risk factors, host immune responses, and pathogenic mechanisms at both the molecular and cellular levels. The recent development of multiomic technologies, including genomics, proteomics, metabolomics, and single-cell transcriptomics, has enabled a fast and panoramic grasp of the pathogen and the disease. Here, we systematically reviewed the major advances in the virology, immunology, and pathogenic mechanisms of SARS-CoV-2 infection that have been achieved via multiomic technologies. Based on well-established cohorts, omics-based methods can greatly enhance the mechanistic understanding of diseases, contributing to the development of new diagnostics, drugs, and vaccines for emerging infectious diseases, such as COVID-19.

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Section: Proteomic/metabolomic Features Associated With Severe Covid-19mentioning

confidence: 99%

Section: Proteomic/metabolomic Features Associated With Severe Covid-19mentioning

confidence: 99%

Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

Wang

Liu

et al. 2021

Cell Mol Immunol

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“…As metabolism has been demonstrated to be intricately related to immunity ( 78 ), we investigated the effects of the anti-TB drugs on the cytokine production by the hMDMs. To determine the effects of the anti-TB drugs on the function of the macrophages, cytokine production by hMDMs after treatment with the two highest concentrations of each drug was assessed in a multiplex assay.…”

Section: Resultsmentioning

confidence: 99%

Host Bioenergetic Parameters Reveal Cytotoxicity of Antituberculosis Drugs Undetected Using Conventional Viability Assays

Cumming

Baig

Addicott

et al. 2021

Antimicrob Agents Chemother

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High attrition rates in tuberculosis (TB) drug development have been largely attributed to safety, which is likely due to the use of endpoint assays measuring cell viability to detect drug cytotoxicity. In drug development of cancer, metabolic and neurological disorders, and antibiotics, cytotoxicity is increasingly being assessed using extracellular flux (XF) analysis, which measures cellular bioenergetic metabolism in real-time. Here, we adopt the XF platform to investigate the cytotoxicity of drugs currently used in TB treatment on the bioenergetic metabolism of HepG2 cells, THP-1 macrophages, and human monocyte derived macrophages (hMDM). We found that the XF analysis reveals earlier drug-induced effects on the cells’ bioenergetic metabolism prior to cell death, measured by conventional viability assays. Furthermore, each cell type has a distinct response to drug treatment, suggesting that more than one cell type should be considered to examine cytotoxicity in TB drug development. Interestingly, chemically unrelated drugs with different modes of action on Mycobacterium tuberculosis have similar effects on the bioenergetic parameters of the cells, thus, discouraging the prediction of potential cytotoxicity based on chemical structure and mode of action of new chemical entities. The clustering of the drug-induced effects on the hMDM bioenergetic parameters are reflected in the clustering of the effects of the drugs on cytokine production in hMDMs, demonstrating concurrence between the effects of the drugs on the metabolism and functioning of the macrophages. These findings can be used as a benchmark to establish XF analysis as a new tool to assay cytotoxicity in TB drug development.

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“…Apart from local interactions, these cells interact and exchange with the cells of the immune system that infiltrate the joints and the tumor sites. Immunometabolism is a relatively new field that is advancing fast, focusing on the interplay between immune cells and their impact on the metabolic processes of the affected cells [ 224 , 225 ]. Development of new methodologies that would allow us to grasp the crosstalks between resident cells and immune cells and map them to downstream effects on the metabolic pathways could open new avenues as to how the immune system can be targeted and modulated to reverse metabolic reprogramming, and vice versa.…”

Section: Perspectivesmentioning

confidence: 99%

Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

Aghakhani

Zerrouk

Niarakis

2020

Cancers

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Fibroblasts, the most abundant cells in the connective tissue, are key modulators of the extracellular matrix (ECM) composition. These spindle-shaped cells are capable of synthesizing various extracellular matrix proteins and collagen. They also provide the structural framework (stroma) for tissues and play a pivotal role in the wound healing process. While they are maintainers of the ECM turnover and regulate several physiological processes, they can also undergo transformations responding to certain stimuli and display aggressive phenotypes that contribute to disease pathophysiology. In this review, we focus on the metabolic pathways of glucose and highlight metabolic reprogramming as a critical event that contributes to the transition of fibroblasts from quiescent to activated and aggressive cells. We also cover the emerging evidence that allows us to draw parallels between fibroblasts in autoimmune disorders and more specifically in rheumatoid arthritis and cancer. We link the metabolic changes of fibroblasts to the toxic environment created by the disease condition and discuss how targeting of metabolic reprogramming could be employed in the treatment of such diseases. Lastly, we discuss Systems Biology approaches, and more specifically, computational modeling, as a means to elucidate pathogenetic mechanisms and accelerate the identification of novel therapeutic targets.

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Immunometabolism: new insights and lessons from antigen-directed cellular immune responses

Cited by 48 publications

References 408 publications

Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

Host Bioenergetic Parameters Reveal Cytotoxicity of Antituberculosis Drugs Undetected Using Conventional Viability Assays

Metabolic Reprogramming of Fibroblasts as Therapeutic Target in Rheumatoid Arthritis and Cancer: Deciphering Key Mechanisms Using Computational Systems Biology Approaches

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