1. Cell Biology

CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens

  1. Jin Wang
  2. Jiayi Xie
  3. Daosong Wang
  4. Xue Han
  5. Minqi Chen
  6. Guojun Shi  Is a corresponding author
  7. Linjia Jiang  Is a corresponding author
  8. Meng Zhao  Is a corresponding author
  1. Sun Yat-sen University, China
https://doi.org/10.7554/eLife.78662
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Cite this article
  1. Jin Wang
  2. Jiayi Xie
  3. Daosong Wang
  4. Xue Han
  5. Minqi Chen
  6. Guojun Shi
  7. Linjia Jiang
  8. Meng Zhao
(2022)
CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens
eLife 11:e78662.
https://doi.org/10.7554/eLife.78662
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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. CXCR4high MKs interacted with myeloid cells to promote their migration and stimulate the bacterial phagocytosis of macrophages and neutrophils by producing TNFα and IL-6. CXCR4high MKs were also capable of phagocytosis, processing and presenting antigens to activate T cells. Furthermore, CXCR4high 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 CXCR4high MKs were generated from infection-induced emergency megakaryopoiesis in response to bacterial infection. Overall, we identify the CXCR4high 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
The following previously published data sets were used

Article and author information

Author details

  1. Jin Wang

    Department of Endocrinology and Metabolism, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Jiayi Xie

    RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  3. 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.

  4. Xue Han

    RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Minqi Chen

    RNA Biomedical Institute, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  6. 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.

  7. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8854-2610

  8. 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.
    ORCID icon "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

© 2022, Wang et al.

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.

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  1. Jin Wang
  2. Jiayi Xie
  3. Daosong Wang
  4. Xue Han
  5. Minqi Chen
  6. Guojun Shi
  7. Linjia Jiang
  8. Meng Zhao
(2022)
CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens
eLife 11:e78662.
https://doi.org/10.7554/eLife.78662

Share this article

https://doi.org/10.7554/eLife.78662

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