Article
Biochemistry & Molecular Biology
Erica Russo, Fabrice Lemaitre, Beatrice Corre, Aleksandra S. Chikina, Francina Langa-Vives, Philippe Bousso
Summary: SPICE-Met is a method for profiling energy metabolism in single cells using flow cytometry or imaging. It can infer the dependence of energy metabolism on oxidative phosphorylation and glycolysis, analyze immune metabolism, and dissect the heterogeneity and plasticity of energy metabolism in single macrophages.
Article
Cell Biology
Vishnu Suresh Babu, Gagan Dudeja, Deepak Sa, Anadi Bisht, Rohit Shetty, Stephane Heymans, Nilanjan Guha, Arkasubhra Ghosh
Summary: Loss of RB1 and HK1 in retinoblastoma reprograms tumor metabolism, enhancing fatty acid oxidation and mitochondrial ATP production instead of glycolysis dependence. These metabolic perturbations could be potential therapeutic targets for retinoblastoma.
Review
Biochemistry & Molecular Biology
Brian S. M. Munansangu, Colin Kenyon, Gerhard Walzl, Andre G. Loxton, Leigh A. Kotze, Nelita du Plessis
Summary: Immunometabolism investigates the interaction between the immune system and metabolic pathways, with small molecules targeting specific pathways to alter immune responses for potential therapeutic interventions. The metabolic reprogramming of MDSC in diseases like cancer contributes to immunosuppression, highlighting the importance of understanding and targeting these pathways in diseases such as tuberculosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Bianca Lima Ferreira, Monica Braganca Sousa, Giuseppe Gianini Figueiredo Leite, Milena Karina Colo Brunialti, Erika Sayuri Nishiduka, Alexandre Keiji Tashima, Tom van der Poll, Reinaldo Salomao
Summary: Metabolic adaptations play a crucial role in shaping immune cell function, particularly in mounting an inflammatory response. In sepsis and endotoxin tolerance, both immune response suppression and activation occur simultaneously. Studies have shown that cellular metabolism, specifically glucose metabolism, is closely related to the modulation of immune responses in these conditions.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Bruno Chausse, Pamela A. Kakimoto, Oliver Kann
Summary: Microglia are sensors of alterations in CNS physiology and undergo metabolic reprogramming to adapt to inflammatory responses. Lipid metabolism in activated microglia plays a crucial role in controlling functions such as migration, phagocytosis, and inflammatory signaling, with disturbances in these processes associated with brain function changes in neuroinflammatory disorders.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Review
Immunology
Yuichi Suwa, Yasuo Nagafuchi, Saeko Yamada, Keishi Fujio
Summary: Dendritic cells (DCs) have important roles in the pathogenesis of rheumatoid arthritis (RA), characterized by chronic synovitis and joint destruction. Conventional dendritic cells (cDCs) in the synovium show enhanced migratory capacities and T cell activation compared to peripheral blood cDCs, while plasmacytoid dendritic cells in RA may have tolerogenic effects. Monocyte-derived dendritic cells (moDCs) in the synovium induce expansion of T-helper 17 cells and proinflammatory cytokine production. Recent studies suggest a link between proinflammatory hypoxic environments in the synovium and metabolic reprogramming of DCs. Targeting the immunometabolism of DCs could be a potential therapeutic approach in RA.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Abigaelle Pelletier, Christian Stockmann
Summary: Innate Lymphoid Cells (ILCs) are key players in regulating tissue homeostasis and early inflammatory responses. They are divided into three groups and five subsets, each characterized by distinct transcription factors, surface markers, and cytokine expression profiles. Environmental signals can trigger the interconversion of subset phenotypes and the plasticity of ILCs, but the role of cellular metabolism in ILC plasticity is still not well understood.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Yue Xu, Yongkang Chen, Xuan Zhang, Jie Ma, Yudong Liu, Liyan Cui, Fang Wang
Summary: Autoimmune diseases are characterized by connective tissue inflammation caused by abnormal autoantibodies. Current treatments for these diseases have side effects, and there is a need to study their pathogenesis to develop selective inhibitors for inflammatory signaling. Immune cells shift their metabolic profile from mitochondrial respiration to glycolysis in these diseases, which is critical to connective tissue inflammation. Glycolysis promotes disease progression by satisfying cellular functions. The impact of glycolysis on the pathophysiological processes of autoimmune diseases and potential therapeutic targets are discussed.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Claudia Barfuesser, Carmen Wiedemann, Anne L. C. Hoffmann, Sieglinde Hirmer, Cornelia A. Deeg
Summary: The study revealed that patients with Equine Recurrent Uveitis (ERU) had a more active metabolic phenotype in their immune cells, showing upregulation of both oxidative phosphorylation and glycolytic pathway. This finding is consistent with other autoimmune diseases and basic research regarding immune cell metabolic alterations.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Alessandra Zevini, Enrico Palermo, Daniele Di Carlo, Magdalini Alexandridi, Serena Rinaldo, Alessio Paone, Francesca Cutruzzola, Marilena P. Etna, Eliana M. Coccia, David Olagnier, John Hiscott
Summary: Dendritic cells play a crucial role in adaptive immune responses. This study reveals that activation of the RIG-I pathway induces metabolic reprogramming in dendritic cells, including increased glycolysis. Inhibition of glycolysis impairs the antiviral activity of dendritic cells and enhances viral replication. These findings highlight the importance of metabolic changes in dendritic cell activation and their impact on antiviral defense.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Li Gao, Yu-xin Liu, Yu-zhi Zhou, Xue-mei Qin
Summary: More and more evidence suggests that metabolic reprogramming is closely linked to Alzheimer's disease (AD). The switch from oxidative phosphorylation to glycolysis worsens microglia-mediated inflammation. Baicalein has been shown to inhibit neuroinflammation in BV-2 microglial cells treated with LPS, but its mechanism of action in relation to glycolysis is unclear. Our results demonstrate that baicalein significantly reduces the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin-2 (PGE2), and tumor necrosis factor (TNF-alpha) in LPS-treated BV-2 cells. H-1-NMR metabolomics analysis reveals that baicalein decreases the levels of lactic acid and pyruvate, and effectively regulates the glycolytic pathway. Further investigation reveals that baicalein inhibits the activity of glycolysis-related enzymes and suppresses STAT3 phosphorylation and c-Myc expression. By using a STAT3 activator, RO8191, we found that baicalein hinders the increase in STAT3 phosphorylation and c-Myc expression triggered by RO8191, and also inhibits the elevated levels of 6-PFK, PK, and LDH caused by RO8191. In conclusion, these findings suggest that baicalein alleviates neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through the STAT3/c-Myc pathway.
NEUROCHEMICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Chiung-Chi Peng, Chang-Rong Chen, Chang-Yu Chen, Kuan-Chou Chen, Robert Y. Peng
Summary: Bicalutamide (Bic) was found to damage both mitochondrial and glycolytic pathways in renal mesangial cells, which may cause renal damage and should be used with caution.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Jonathan R. Erlich, Eunice E. To, Raymond Luong, Felicia Liong, Stella Liong, Osezua Oseghale, Mark A. Miles, Steven Bozinovski, Robert D. Brooks, Ross Vlahos, Stanley Chan, John J. O'Leary, Doug A. Brooks, Stavros Selemidis
Summary: The study reveals that macrophages undergo a metabolic switch from oxidative phosphorylation to glycolysis when exposed to gram-negative bacterial lipopolysaccharide (LPS). This switch modulates antibacterial host defence mechanisms by increasing the activity of NOX2 enzyme and promoting the expression of type I IFN-beta. Both glycolysis and the pentose phosphate pathway play important roles in promoting LPS-induced inflammation in macrophages.
Review
Biochemistry & Molecular Biology
Mohd Hatimi Tukiman, Mohd Nor Norazmi
Summary: Tuberculosis remains a major threat to global public health. This review seeks to explore the mucosal immunometabolism of resident effector cells in response to Mtb infection and how Mtb manipulates them for its survival and growth, with the aim of filling knowledge gaps and potentially contributing to future vaccination and therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Elisa M. York, Jingfei Zhang, Hyun B. Choi, Brian A. MacVicar
Summary: Immunometabolism refers to the restructuring of metabolic pathways in response to immune stimulation and their ability to control immune functions. By studying individual microglia within acute hippocampal slices, researchers found that LPS-induced glycolysis in microglia was necessary for stabilizing HIF-1 alpha and producing the proinflammatory cytokine IL-1 beta, which in turn inhibited the formation of synaptic LTP. Blunting microglial glycolysis with 2DG not only rescued LTP in LPS-stimulated slices but also inhibited HIF-1 alpha accumulation and IL-1 beta production. These findings highlight the importance of metabolic reprogramming in regulating microglial immune functions and their impact on cytokine release and neuronal activity.
Article
Biochemistry & Molecular Biology
Christian Marx, Marc U. Schaarschmidt, Joanna Kirkpatrick, Lisa Marx-Bluemel, Melisa Halilovic, Martin Westermann, Doerte Hoelzer, Felix B. Meyer, Yibo Geng, Katrin Buder, Hauke M. Schadwinkel, Kanstantsin Siniuk, Sabine Becker, Rene Thierbach, James F. Beck, Juergen Sonnemann, Zhao-Qi Wang
Summary: The study suggests that combination treatment with HSP90 inhibitor and ATR inhibitor may be an effective therapeutic approach for Ewing's sarcoma, regardless of the p53 status.
CELL AND BIOSCIENCE
(2021)
Article
Oncology
Christian Marx, Juergen Sonnemann, Mandy Beyer, Oliver D. K. Maddocks, Sergio Lilla, Irene Hauzenberger, Andrea Piee-Staffa, Kanstantsin Siniuk, Suneetha Nunna, Lisa Marx-Bluemel, Martin Westermann, Tobias Wagner, Felix B. Meyer, Rene Thierbach, Christina S. Mullins, Said Kdimati, Michael Linnebacher, Francesco Neri, Thorsten Heinzel, Zhao-Qi Wang, Oliver H. Kraemer
Summary: Acetylation of p53, specifically at the C-terminal, controlled by HDACs, plays a crucial role in determining cellular stress responses and apoptosis in p53-positive CRC cells. The combination of irinotecan and entinostat represents clinically tractable agents for the therapy of p53-proficient CRC due to this mechanism.
MOLECULAR ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Murat Kirtay, Josefine Sell, Christian Marx, Holger Haselmann, Mihai Ceanga, Zhong-Wei Zhou, Vahid Rahmati, Joanna Kirkpatrick, Katrin Buder, Paulius Grigaravicius, Alessandro Ori, Christian Geis, Zhao-Qi Wang
Summary: ATR, a key regulator of DNA damage response and replication stress, also plays a role in regulating neuronal activity beyond its known functions. Deletion of ATR in neurons leads to increased intrinsic activity, aberrant firing, and heightened epileptiform activity, potentially increasing susceptibility to ataxia and epilepsy.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Simone Di Sanzo, Katrin Spengler, Anja Leheis, Joanna M. Kirkpatrick, Theresa L. Raendler, Tim Baldensperger, Therese Dau, Christian Henning, Luca Parca, Christian Marx, Zhao-Qi Wang, Marcus A. Glomb, Alessandro Ori, Regine Heller
Summary: Posttranslational mechanisms, specifically modification by advanced glycation end products such as carboxymethyllysine, play a key role in cellular protein abundance and function. The authors identified over 1000 sites of protein carboxymethylation and demonstrated that this modification affects protein homeostasis and cell proliferation, providing insights into the molecular roles of advanced glycation end products during aging.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lisa Marx-Bluemel, Christian Marx, Jurgen Sonnemann, Frank Weise, Jorg Hampl, Jessica Frey, Linda Rothenburger, Emilio Cirri, Norman Rahnis, Philipp Koch, Marco Groth, Andreas Schober, Zhao-Qi Wang, James F. Beck
Summary: By combining artificial 3D PDMS scaffolds with optimized HSC culture medium, high numbers of undifferentiated HSCs can be amplified in vitro, activating key molecular signaling pathways that promote HSC expansion and maintenance of pluripotency.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Trim Lajqi, Natascha Koestlin-Gille, Stefan Hillmer, Maylis Braun, Simon A. Kranig, Stefanie Dietz, Christian Krause, Jessica Ruehle, David Frommhold, Johannes Poeschl, Christian Gille, Hannes Hudalla
Summary: Research has shown that small extracellular vesicles from the gut can mediate adaptive responses in neutrophils in vitro. Low-dose stimulation enhances neutrophils' pro-inflammatory sensitivity and activity, while high-dose stimulation leads to a tolerant phenotype.
Article
Biochemistry & Molecular Biology
Alena Gschwind, Christian Marx, Marie D. Just, Paula Severin, Hannah Behring, Lisa Marx-Blumel, Sabine Becker, Linda Rothenburger, Martin Foester, James F. Beck, Juergen Sonnemann
Summary: This study identified the relationship between autophagy and the cell cycle, and provided clear evidence of high autophagy in G2/M-phase cells using the Cyto-ID technique.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Cell Biology
Trim Lajqi, David Frommhold, Christian Gille, Hannes Hudalla
Summary: Innate immune cells have the potential to develop immunological memory through a process called trained immunity. This process is characterized by increased production of inflammatory mediators and changes in cellular functions. We have established a two-hit stimulation protocol in vitro to induce memory-like responses in murine bone marrow neutrophils. This protocol can be used to study the evolving field of memory-like innate immunity. Pathogen-associated molecular patterns (PAMPs) promote dose-dependent contrasting memory-like responses.
CELLULAR IMMUNOLOGY
(2022)
Article
Pediatrics
Christiane Schlegel, Kai Liu, Barbel Spring, Stefanie Dietz, Christian F. Poets, Hannes Hudalla, Trim Lajqi, Natascha Koestlin-Gille, Christian Gille
Summary: This study compares the differences between adult and neonatal immune cells under low oxygen partial pressure. It finds that HIF-1 alpha expression, phagocytosis, ROS production, and VEGF secretion are significantly reduced in neonatal immune cells under hypoxic conditions. This may contribute to the decreased responsiveness of neonatal immune cells in the context of infection.
PEDIATRIC RESEARCH
(2023)
Article
Cell Biology
Leonie K. Stabenow, Darya Zibrova, Claudia Ender, Dario L. Helbing, Katrin Spengler, Christian Marx, Zhao-Qi Wang, Regine Heller
Summary: Vascular aging is associated with endothelial dysfunction, which is influenced by the accumulation of senescent cells in aged tissues and their environment. Senescence is closely linked to changes in cell metabolism, with senescent cells showing enhanced glycolytic and oxidative glucose metabolism.
Article
Oncology
Christian Marx, Juergen Sonnemann, Oliver D. K. Maddocks, Lisa Marx-Bluemel, Mandy Beyer, Doerte Hoelzer, Rene Thierbach, Claudia Maletzki, Michael Linnebacher, Thorsten Heinzel, Oliver H. Kraemer
Summary: Chemotherapeutics that cause DNA replication stress increase the metabolism of colorectal cancer (CRC) cells, and glucose restriction might improve the effectiveness of classical chemotherapy against p53-positive cells.
CANCER & METABOLISM
(2022)
Article
Immunology
Julian Schwarz, Jessica Ruehle, Kevin Stephan, Stefanie Dietz, Janina Geissert, Ulrich Schoppmeier, Julia S. Frick, Hannes Hudalla, Trim Lajqi, Christian F. Poets, Christian Gille, Natascha Koestlin-Gille
Summary: The newborn's immune system faces the challenge of fighting off infectious agents and tolerating commensals without excessive inflammation. Myeloid-derived suppressor cells (MDSC) play a role in fetal-maternal tolerance and intestinal inflammation regulation in neonates. The role of MDSC in microbiome establishment has not been investigated. In a mouse model, deletion of HIF-1α in myeloid cells resulted in reduced MDSC expansion, altered microbiome composition, and intestinal T-cell homeostasis, suggesting a role of MDSC in inflammation regulation and microbiome establishment during the neonatal period.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jessica Ruehle, Marco Ginzel, Stefanie Dietz, Julian Schwarz, Trim Lajqi, Sandra Beer-Hammer, Christian F. Poets, Christian Gille, Natascha Koestlin-Gille
Summary: Newborns, especially preterm infants, are more susceptible to infections due to their immature immune system. In particular, neonatal neutrophils have an immunomodulatory effect on T-cells. This study investigated the role of neonatal neutrophils in T-cell development in the thymus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Trim Lajqi, Natascha Koestlin-Gille, Reinhard Bauer, Sotirios G. Zarogiannis, Esra Lajqi, Valdrina Ajeti, Stefanie Dietz, Simon A. Kranig, Jessica Ruehle, Ardian Demaj, Janine Hebel, Maria Bartosova, David Frommhold, Hannes Hudalla, Christian Gille
Summary: For almost a century, memory functions were believed to belong to acquired immune cells. However, recent studies have challenged this paradigm, revealing that innate immune cells also possess memory-like features (known as trained immunity). On the other hand, endotoxin tolerance, a state of immunosuppression in myeloid cells, reduces their inflammatory capacity. Both trained immunity and endotoxin tolerance are accompanied by epigenetic and metabolic changes in cells. Inappropriate induction of these adaptive cues can promote susceptibility to secondary infections or contribute to the progression of inflammatory disorders.
