HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease.
HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease.
复制标题
肺COVID-19疾病期间的HLA依赖性异质性和巨噬细胞免疫蛋白酶体激活。
DOI：
10.1186/s12967-021-02965-5
复制
发表时间：
2021-07-05
影响因子：
7.4
通讯作者：
Griscelli F
中科院分区：
文献类型：
--
作者：
Desterke C;Turhan AG;Bennaceur-Griscelli A;Griscelli F
由SARS-CoV-2病毒引起的全球大流行的特征是症状的显著和不可预测的异质性，这仍然知之甚少。将COVID 19肺组织的转录组和单细胞转录组与抗SARS-COV 2蛋白质组的MHC I类免疫肽组的深入分析相结合。对COVID-19患者肺样本的转录组分析显示，这些组织中MHC I类抗原呈递的激活与SARS-CoV-2 RNA的存在量相关。类似地，在这些样本中检测到SARS-CoV-2水平与位于6p21.32区域（40 kb长，在MHC-II簇内）的编码免疫蛋白酶体组分的基因组簇的表达之间的正相关。对支气管肺泡细胞的单细胞转录组的分析强调了COVID-19患者的CD 68 + M1巨噬细胞中免疫蛋白酶体的激活，以及这些细胞中基于PSMB 8的轨迹，其特征是在轻度疾病期间激活防御反应，以及在严重COVID-19期间损害肺泡清除机制。通过检测SARS-CoV-2免疫肽组与全世界最常见的HLA-A、-B和-C等位基因的结合亲和力，我们发现A型等位基因和亚洲人群中更强的呈递者数量更高，这可能有助于解释为什么这种疾病现在在世界这一地区不那么普遍。肺COVID-19疾病期间巨噬细胞免疫蛋白酶体激活的HLA依赖性异质性可能对预测全球人群对HLA依赖性SARS-CoV-2疫苗的反应具有影响。在线版本包含补充材料，可通过10.1186/s12967-021-02965-5获得。
The worldwide pandemic caused by the SARS-CoV-2 virus is characterized by significant and unpredictable heterogeneity in symptoms that remains poorly understood. Transcriptome and single cell transcriptome of COVID19 lung were integrated with deeplearning analysis of MHC class I immunopeptidome against SARS-COV2 proteome. An analysis of the transcriptomes of lung samples from COVID-19 patients revealed that activation of MHC class I antigen presentation in these tissues was correlated with the amount of SARS-CoV-2 RNA present. Similarly, a positive relationship was detected in these samples between the level of SARS-CoV-2 and the expression of a genomic cluster located in the 6p21.32 region (40 kb long, inside the MHC-II cluster) that encodes constituents of the immunoproteasome. An analysis of single-cell transcriptomes of bronchoalveolar cells highlighted the activation of the immunoproteasome in CD68 + M1 macrophages of COVID-19 patients in addition to a PSMB8-based trajectory in these cells that featured an activation of defense response during mild cases of the disease, and an impairment of alveolar clearance mechanisms during severe COVID-19. By examining the binding affinity of the SARS-CoV-2 immunopeptidome with the most common HLA-A, -B, and -C alleles worldwide, we found higher numbers of stronger presenters in type A alleles and in Asian populations, which could shed light on why this disease is now less widespread in this part of the world. HLA-dependent heterogeneity in macrophage immunoproteasome activation during lung COVID-19 disease could have implications for efforts to predict the response to HLA-dependent SARS-CoV-2 vaccines in the global population. The online version contains supplementary material available at 10.1186/s12967-021-02965-5.
登录
查看更多内容
DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
影响因子：
5.8
作者：
Desterke C;Turhan AG;Bennaceur-Griscelli A;Griscelli F
通讯作者：
Griscelli F
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG
影响因子：
64.5
作者：
Huber, Eva M.;Basler, Michael;Groll, Michael
通讯作者：
Groll, Michael