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 |
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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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