Kynurenic acid may underlie sex-specific immune responses to COVID-19.
Kynurenic acid may underlie sex-specific immune responses to COVID-19.
复制标题
DOI：
10.1126/scisignal.abf8483
复制
发表时间：
2021-07-06
影响因子：
7.3
通讯作者：
Johnson CH
中科院分区：
文献类型：
--
作者：
Cai Y;Kim DJ;Takahashi T;Broadhurst DI;Yan H;Ma S;Rattray NJW;Casanovas-Massana A;Israelow B;Klein J;Lucas C;Mao T;Moore AJ;Muenker MC;Oh JE;Silva J;Wong P;Yale IMPACT Research team;Ko AI;Khan SA;Iwasaki A;Johnson CH
与女性相比，男性COVID-19患者具有更多的犬尿烯酸，这可能是他们免疫反应较差的原因。男性和女性对SARS-CoV-2感染有不同的免疫反应，男性是死亡的危险因素，特别是在老年人中。Cai等人对COVID-19患者和未感染的医护人员的血清进行了代谢组学分析，并确定了17种与疾病相关的代谢物。然而，仅在男性COVID-19患者中，色氨酸代谢物犬尿烯酸（KA）的量与年龄，炎症和疾病结果相关。KA抑制谷氨酸释放，并且在恶化的患者中谷氨酸丰度降低。总之，这些发现表明KA与对COVID-19的免疫反应的性别特异性差异有关，这表明它可能针对男性患者。2019冠状病毒病（COVID-19）在男性中的临床结果比女性差，免疫反应是这些性别相关差异的基础。由于免疫反应在一定程度上受到代谢物的调节，因此我们检查了COVID-19患者的血清代谢组。在男性患者中，犬尿烯酸（KA）和高KA-犬尿氨酸（K）比（KA：K）与年龄和炎性细胞因子和趋化因子呈正相关，与T细胞反应呈负相关。临床恶化的男性比稳定的男性有更高的KA：K。KA抑制谷氨酸释放，临床恶化和与免疫反应相关的患者中谷氨酸丰度较低。基因型-组织表达（GTEx）项目的数据分析显示，编码产生KA的酶（犬尿氨酸转氨酶）的基因表达与老年男性的细胞因子丰度和免疫应答激活相关。这项研究表明，KA与COVID-19中的免疫反应和临床结果具有性别特异性联系，表明男性代谢产物和免疫反应之间存在正反馈。
Compared to females, male COVID-19 patients have more kynurenic acid, which may underlie their poorer immune response. Males and females have different immune responses to SARS-CoV-2 infection, with male sex being a risk factor for mortality, particularly among older individuals. Cai et al. performed metabolomics analysis of serum from COVID-19 patients and uninfected health care workers and identified 17 metabolites that were associated with the disease. However, in male COVID-19 patients only, the amount of the tryptophan metabolite kynurenic acid (KA) correlated with age, inflammation, and disease outcome. KA inhibits glutamate release, and glutamate abundance was reduced in patients who deteriorated. Together, these findings indicate that KA is associated with sex-specific differences in immune responses to COVID-19, suggesting that it might be targeted in male patients. Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males.
登录
查看更多内容
DOI：
10.1006/bbrc.1999.0367
发表时间：
1999-03-24
影响因子：
3.1
作者：
Jana, NR;Sarkar, S;Sone, H
通讯作者：
Sone, H
影响因子：
7.3
作者：
Jacob, Aude;Hartz, Anika M. S.;Decleves, Xavier
通讯作者：
Decleves, Xavier
影响因子：
64.8
作者：
Lucas, Carolina;Wong, Patrick;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko
影响因子：
5.2
作者：
de Souza, Camila Oliveira;Valenzuela, Carina A.;Calder, Philip C.
通讯作者：
Calder, Philip C.
DOI：
10.1007/978-3-7091-0888-8_4
发表时间：
2012-01-01
期刊：
NERVE-DRIVEN IMMUNITY: NEUROTRANSMITTERS AND NEUROPEPTIDES IN THE IMMUNE SYSTEM
影响因子：
--
作者：
Ganor, Yonatan;Levite, Mia
通讯作者：
Levite, Mia