TY - JOUR TI - CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens AU - Wang, Jin AU - Xie, Jiayi AU - Wang, Daosong AU - Han, Xue AU - Chen, Minqi AU - Shi, Guojun AU - Jiang, Linjia AU - Zhao, Meng A2 - Rehman, Jalees A2 - van der Meer, Jos W A2 - Rehman, Jalees VL - 11 PY - 2022 DA - 2022/07/29 SP - e78662 C1 - eLife 2022;11:e78662 DO - 10.7554/eLife.78662 UR - https://doi.org/10.7554/eLife.78662 AB - 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 inflammatory 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. KW - hematopoietic stem cell KW - host-defense immunity KW - megakaryocytes KW - megakaryopoiesis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -