CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens

Abstract
Data availability
Article and author information
Metrics

Abstract

Megakaryocytes (MKs) continuously produce platelets to support hemostasis and form a niche for hematopoietic stem cell maintenance in the bone marrow. MKs are also involved in inflammation responses; however, the mechanism remains poorly understood. Using single-cell sequencing, we identified a CXCR4 highly expressed MK subpopulation, which exhibited both MK-specific and immune characteristics. CXCR4^high MKs interacted with myeloid cells to promote their migration and stimulate the bacterial phagocytosis of macrophages and neutrophils by producing TNFα and IL-6. CXCR4^high MKs were also capable of phagocytosis, processing and presenting antigens to activate T cells. Furthermore, CXCR4^high MKs also egressed circulation and infiltrated into the spleen, liver, and lung upon bacterial infection. Ablation of MKs suppressed the innate immune response and T cell activation to impair the anti-bacterial effects in mice under the Listeria monocytogenes challenge. Using hematopoietic stem/progenitor cell lineage-tracing mouse lines, we show that CXCR4^high MKs were generated from infection-induced emergency megakaryopoiesis in response to bacterial infection. Overall, we identify the CXCR4^high MKs, which regulate host-defense immune response against bacterial infection.

Data availability

The scRNA-seq data generated in this study are deposited in GEO (GSE168224, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168224). The code used in the study can be accessed at GitHub (https://https://github.com/JYCathyXie/MK_infection).

The following data sets were generated

1. Zhao M
2. Wang J
3. Xie J
4. Wang D
5. Han X
(2022) Megakaryocyte derived immunoregulatory cells regulate host-defense immunity against bacterial pathogens
NCBI Gene Expression Omnibus, GSE168224.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168224

The following previously published data sets were used

(2021) Single Cell Transcriptomic Analysis of Lung and Hematopoietic Megakaryocytes from Embryonic and Adult Mice.
NCBI Gene Expression Omnibus, GSE152574.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152574
1. Pariser DN
2. Hilt ZT
3. Ture SK
4. Blick-Nitko SK
5. Looney MR
6. Cleary SJ
7. Roman-Pagan E
8. Saunders J
9. Georas SN
10. Veazey J
11. Madera F
12. Santos LT
13. Arne A
14. Huynh NT
15. Livada AC
16. Guerrero-Martin SM
17. Lyons C
18. Metcalf-Pate KA
19. McGrath KE
20. Palis J
21. Morrell CN
(2020) Lung Megakaryocytes are Immune Modulatory Cells
NCBI Gene Expression Omnibus, GSE158358.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE158358
1. Xie X
2. Shi Q
3. Wu P
4. Zhang X
(2020) Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection
NCBI Gene Expression Omnibus, GSE137540.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137540
1. Hamey FK
2. Lau WW
3. Diamanti E
4. Göttgens B
5. Dahlin JS
(2020) Single-cell RNA sequencing of basophils from mouse bone marrow
NCBI Gene Expression Omnibus, GSE128074.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE128074
1. Tabula Muris Consortium
(2019) Expression profiling by high throughput sequencing
NCBI Gene Expression Omnibus, GSE132042.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132042

Article and author information

Author details

Jin Wang

Department of Endocrinology and Metabolism, Sun Yat-sen University, Guangzhou, China

Competing interests
The authors declare that no competing interests exist.
Jiayi Xie

RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China

Competing interests
The authors declare that no competing interests exist.
Daosong Wang

Key Laboratory of Stem Cells and Tissue Engineering, Sun Yat-sen University, Guangzhou, China

Competing interests
The authors declare that no competing interests exist.
Xue Han

RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China

Competing interests
The authors declare that no competing interests exist.
Minqi Chen

RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China

Competing interests
The authors declare that no competing interests exist.
Guojun Shi

Department of Endocrinology and Metabolism, Sun Yat-sen University, Guangzhou, China

For correspondence
shigj6@mail.sysu.edu.cn

Competing interests
The authors declare that no competing interests exist.
Linjia Jiang

RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China

For correspondence
jianglj7@mail.sysu.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8854-2610
Meng Zhao

RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China

For correspondence
zhaom38@mail.sysu.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7909-7594

Funding

National Key Research and Development Program of China (2018YFA0107200)

Meng Zhao

National Natural Science Foundation of China (82170112)

Meng Zhao

National Natural Science Foundation of China (81900101)

Jin Wang

China Postdoctoral Science Foundation (2021M693614)

Jin Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were performed according to protocols approved by theInstitutional Animal Care and Use Committee.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.