Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications

Autor: Na Chen, Nan Xiao, Quanxin Long, Huanhuan Pang, Xiangjun Meng, Zeping Hu, Ailong Huang, Jieli Hu, Meng Nie, Ni Tang, Ke Li, Xiaorong Ran, Bohong Wang, Haijun Deng, Shao Li
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Chemokine
Science
medicine.medical_treatment
General Physics and Astronomy
In Vitro Techniques
Peripheral blood mononuclear cell
Article
General Biochemistry
Genetics and Molecular Biology
Proinflammatory cytokine
Cohort Studies
Prognostic markers
03 medical and health sciences
0302 clinical medicine
Immune system
Metabolome
Metabolomics
Animals
Humans
Medicine
Longitudinal Studies
Purine metabolism
Pandemics
Multidisciplinary
biology
SARS-CoV-2
business.industry
COVID-19
General Chemistry
medicine.disease
Macaca mulatta
Cytokine release syndrome
030104 developmental biology
Cytokine
Case-Control Studies
Immunology
Leukocytes
Mononuclear
biology.protein
Cytokines
Female
Inflammation Mediators
Cytokine Release Syndrome
business
Metabolic Networks and Pathways
030217 neurology & neurosurgery
Follow-Up Studies
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021)
ISSN: 2041-1723
Popis: Cytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.
Metabolism changes can modulate immune responses in many contexts, and vice versa. Here the authors associate metabolomic, as well as cytokine and chemokine, data from stratified COVID-19 patients to find that arginine, tryptophan and purine metabolic pathways correlate with hyperproliferation, thus hinting at potential therapeutic targets for severe COVID-19 patients.
Databáze: OpenAIRE
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