CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens
- Sun Yat-sen University, China
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).
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Megakaryocyte derived immunoregulatory cells regulate host-defense immunity against bacterial pathogensNCBI Gene Expression Omnibus, GSE168224.
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Single Cell Transcriptomic Analysis of Lung and Hematopoietic Megakaryocytes from Embryonic and Adult Mice.NCBI Gene Expression Omnibus, GSE152574.
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Lung Megakaryocytes are Immune Modulatory CellsNCBI Gene Expression Omnibus, GSE158358.
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Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infectionNCBI Gene Expression Omnibus, GSE137540.
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Single-cell RNA sequencing of basophils from mouse bone marrowNCBI Gene Expression Omnibus, GSE128074.
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Expression profiling by high throughput sequencingNCBI Gene Expression Omnibus, GSE132042.
Article and author information
Author details
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.
Reviewing Editor
- Jalees Rehman, University of Illinois at Chicago, United States
Ethics
Animal experimentation: All animal experiments were performed according to protocols approved by theInstitutional Animal Care and Use Committee.
Version history
- Preprint posted: June 10, 2021 (view preprint)
- Received: March 15, 2022
- Accepted: July 28, 2022
- Accepted Manuscript published: July 29, 2022 (version 1)
- Version of Record published: August 12, 2022 (version 2)
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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CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens
eLife 11:e78662.
https://doi.org/10.7554/eLife.78662
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