CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens
Jin Wang, Jiayi Xie, Daosong Wang, Xue Han, Minqi Chen, Guojun Shi, Linjia Jiang, Meng Zhao
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 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. 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.