Pulmonary Megakaryocytes Orchestrate Host Defense via PcrV-Induced NF-?B Signaling in Pseudomonas aeruginosa Infection
Megakaryocytes, traditionally known for their role in platelet production, have recently emerged as key players in immune responses during infections. In this study, we explore the involvement of pulmonary Megakaryocytes in the response to P. aeruginosa infection, with a specific focus on the mechanistic activation of Megakaryocytes via bacterial toxins. We demonstrate that P. aeruginosa infection triggers significant alterations in chemokine signaling and NF-?B pathways in pulmonary Megakaryocytes, leading to the upregulation of pro-inflammatory cytokines and chemotactic factors. Activated pulmonary Megakaryocytes effectively promote the recruitment of phagocytes, enhancing the host's resistance to P. aeruginosa infection. we identify PcrV as a key NF-?B activator in Mmegakaryocytes, evidenced by elevated expression of inflammatory markers and chemokines in response to PcrV. Inhibition of NF-?B signaling dampens this inflammatory response, confirming its critical role in megakaryocyte activation. Our findings provide novel insights into the immune function of megakaryocytes as active modulators during bacterial infections. This research highlights the complex interaction between megakaryocytes and phagocytes, suggesting a new approach for managing infectious diseases by modulating megakaryocyte activity to control bacterial pneumonia. Overall design: After constructing an acute pneumonia mouse model with or without PAO1 strain, RNA seq analysis was performed to sort lung MKs using flow cytometry. Two samples were sent to each group for SMART sequencing.