CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens

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 TNF alpha 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.

Automated summary

Using single-cell sequencing, researchers identified a specific subpopulation of megakaryocytes (MKs) that highly expressed CXCR4 and exhibited both immune characteristics and MK-specific features. These CXCR4(high) MKs interacted with myeloid cells to promote their migration and enhance bacterial phagocytosis, and they were also capable of antigen presentation to activate T cells. Furthermore, in response to bacterial infection, these CXCR4(high) MKs could exit circulation and infiltrate into the spleen, liver, and lung. The ablation of MKs suppressed the innate immune response and impaired the anti-bacterial effects of T cells in mice.