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bioRxiv · 10.1101/2021.06.09.447810

Megakaryocyte derived immune-stimulating cells regulate host-defense immunity against bacterial pathogens

Wang, J.·Xie, J.·Han, X.·Wang, D.·Chen, M.·Jiang, L.·Zhao, M.
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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. Here, using single-cell sequencing we identified an MK-derived immune-stimulating cell (MDIC) population exhibiting both MK-specific and immune characteristics, which highly expresses CXCR4 and immune response genes to participate in host-protective response against bacteria. MDICs interact with myeloid cells to promote their migration and stimulate the bacterial phagocytosis of macrophages and neutrophils by producing TNF and IL-6. CXCR4high MDICs egress circulation and infiltrate into the spleen, liver, and lung upon bacterial infection. Ablation of MKs suppresses 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 line, we show that MDICs are generated from infection-induced emergency megakaryopoiesis in response to bacterial infection. Overall, we identify MDICs as an MK subpopulation, which regulates host-defense immune response against bacterial infection.

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Wang, J., Xie, J., Han, X., Wang, D., Chen, M., Jiang, L., Zhao, M.. 2021-06-10. Megakaryocyte derived immune-stimulating cells regulate host-defense immunity against bacterial pathogens. https://doi.org/10.1101/2021.06.09.447810

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