Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications.
Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications.
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综合细胞因子和代谢物分析揭示了COVID-19患者的免疫代谢重编程及其治疗意义。
DOI：
10.1038/s41467-021-21907-9
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发表时间：
2021-03-12
影响因子：
16.6
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Xiao N;Nie M;Pang H;Wang B;Hu J;Meng X;Li K;Ran X;Long Q;Deng H;Chen N;Li S;Tang N;Huang A;Hu Z
细胞因子释放综合征是新冠肺炎重症患者感染SARS-CoV-2引起多器官损害和致死结局的主要原因。新陈代谢可以调节针对传染病的免疫反应，但我们对宿主新陈代谢如何与炎症反应相关并影响新冠肺炎患者细胞因子释放的了解仍然有限。在这里，我们对来自健康对照组、轻度和重度新冠肺炎患者的血清样本进行代谢组学和细胞因子/趋化因子图谱分析，并描绘他们的全球代谢和免疫反应图景。相关分析表明，代谢产物与促炎细胞因子/趋化因子，如IL-6、M-CSF、IL-1α、IL-1β密切相关，提示精氨酸、色氨酸、嘌呤代谢与炎症反应之间存在潜在的调控串扰。重要的是，我们还证明了靶向代谢显著调节从体外感染SARS-CoV-2的恒河猴外周血中分离的单个核细胞释放促炎细胞因子，暗示利用代谢变化可能是治疗新冠肺炎致死性CRS的潜在策略。新陈代谢的变化可以在许多情况下调节免疫反应，反之亦然。在这里，作者关联了来自分层新冠肺炎患者的代谢组以及细胞因子和趋化因子的数据，发现精氨酸、色氨酸和嘌呤代谢途径与过度增殖相关，从而暗示了重症新冠肺炎患者的潜在治疗靶点。
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.
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Itaconate连接琥珀酸脱氢酶与巨噬细胞代谢重塑和调节炎症的联系。
影响因子：
29
作者：
Lampropoulou V;Sergushichev A;Bambouskova M;Nair S;Vincent EE;Loginicheva E;Cervantes-Barragan L;Ma X;Huang SC;Griss T;Weinheimer CJ;Khader S;Randolph GJ;Pearce EJ;Jones RG;Diwan A;Diamond MS;Artyomov MN
通讯作者：
Artyomov MN
影响因子：
64.5
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
通讯作者：
Barouch DH
影响因子：
29
作者：
Codo, Ana Campos;Davanzo, Gustavo Gastao;Moraes-Vieira, Pedro M.
通讯作者：
Moraes-Vieira, Pedro M.
影响因子：
3.8
作者：
Lee, Andrew C. Y.;To, Kelvin K. W.;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung
影响因子：
82.9
作者：
Del Valle DM;Kim-Schulze S;Huang HH;Beckmann ND;Nirenberg S;Wang B;Lavin Y;Swartz TH;Madduri D;Stock A;Marron TU;Xie H;Patel M;Tuballes K;Van Oekelen O;Rahman A;Kovatch P;Aberg JA;Schadt E;Jagannath S;Mazumdar M;Charney AW;Firpo-Betancourt A;Mendu DR;Jhang J;Reich D;Sigel K;Cordon-Cardo C;Feldmann M;Parekh S;Merad M;Gnjatic S
通讯作者：
Gnjatic S