HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease

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Abstract

Background

The worldwide pandemic caused by the SARS-CoV-2 virus is characterized by significant and unpredictable heterogeneity in symptoms that remains poorly understood.

Methods

Transcriptome and single cell transcriptome of COVID19 lung were integrated with deeplearning analysis of MHC class I immunopeptidome against SARS-COV2 proteome.

Results

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.

Conclusions

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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12967-021-02965-5.

Related collections

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Author and article information

Contributors

Frank Griscelli: franck.griscelli@gustaveroussy.fr

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 5 July 2021

Publication date PMC-release: 5 July 2021

Publication date Collection: 2021

Volume: 19

Electronic Location Identifier: 290

Affiliations

[1 ]INSERM UA9- University Paris-Saclay, 94800 Villejuif, France

[2 ]GRID grid.460789.4, ISNI 0000 0004 4910 6535, ESTeam Paris Sud, INGESTEM National IPSC Infrastructure, University Paris-Saclay, ; 94800 Villejuif, France

[3 ]GRID grid.413784.d, ISNI 0000 0001 2181 7253, Division of Hematology, , Kremlin-Bicetre Hospital, ; 94270 Kremlin Bicetre, France

[4 ]University Paris Saclay, Faculty of Medicine, 94275 Le Kremlin Bicêtre, France

[5 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, University of Paris, Faculty Sorbonne Paris Cité, Faculté Des Sciences Pharmaceutiques Et Biologiques, ; Paris, France

[6 ]GRID grid.14925.3b, ISNI 0000 0001 2284 9388, Department of Biopathology, , Gustave-Roussy Cancer Institute, ; 94800 Villejuif, France

[7 ]GRID grid.413133.7, ISNI 0000 0001 0206 8146, INSERM UA9, Institut André Lwoff, Hôpital Paul Brousse, ; Bâtiment A CNRS, 7 rue Guy Moquet, 94802 Villejuif, France

Article

Publisher ID: 2965

DOI: 10.1186/s12967-021-02965-5

PMC ID: 8256232

PubMed ID: 34225749

SO-VID: 93deac31-47aa-47ec-ae8f-9d630d53afdf

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 23 February 2021

Date accepted : 27 June 2021

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: covid-19,macrophage,immunoproteasome,hla,peptidome,antigen presentation,transcriptome,integrative analysis,mhc class-i

Data availability:

ScienceOpen disciplines: Medicine

Keywords: covid-19, macrophage, immunoproteasome, hla, peptidome, antigen presentation, transcriptome, integrative analysis, mhc class-i