Beyond Thrombopoiesis: The Immune Functions of Megakaryocytes in Bacterial Infections and Sepsis.

Megakaryocytes (MKs) are specialized hematopoietic cells long recognized for their ability to produce platelets. Increasing evidence now highlights MKs as multifunctional immune effectors that bridge hematopoiesis with host immunity. In the bone marrow (BM), MKs arise through thrombopoietin (TPO)-mediated differentiation of hematopoietic stem cells (HSCs) and show substantial heterogeneity, with discrete subsets specialized for platelet production (thrombopoiesis), HSC niche maintenance, or immune modulation. Outside the BM, MKs in the lungs and spleen perform tissue-specific immune functions, including pathogen recognition, phagocytosis, antigen presentation, and secretion of cytokines. During bacterial infections and sepsis, infectious or inflammatory cues reprogram MKs to amplify immune signaling and host responses, but can also drive coagulopathy and contribute to organ failure. Collectively, these findings redefine MKs as dynamic immunomodulatory cells positioned at the interface of thrombopoiesis and innate and adaptive immunity. In this review, we synthesize emerging literature on MK biogenesis, functional diversity, and immune modulation, with a special focus on their roles in bacterial infections and sepsis.