Platelet and Megakaryocyte Roles in Innate and Adaptive Immunity

Abstract

Classically, platelets have been described as the cellular blood component that mediates hemostasis and thrombosis. This important platelet function has received significant research attention for >150 years. The immune cell functions of platelets are much less appreciated. Platelets interact with and activate cells of all branches of immunity in response to pathogen exposures and infection, as well as in response to sterile tissue injury. In this review, we focus on innate immune mechanisms of platelet activation, platelet interactions with innate immune cells, as well as the intersection of platelets and adaptive immunity. The immune potential of platelets is dependent in part on their megakaryocyte precursor providing them with the molecular composition to be first responders and immune sentinels in initiating and orchestrating coordinated pathogen immune responses. There is emerging evidence that extramedullary megakaryocytes may be immune differentiated compared with bone marrow megakaryocytes, but the physiological relevance of immunophenotypic differences are just beginning to be explored. These concepts are also discussed in this review. The immune functions of the megakaryocyte/platelet lineage have likely evolved to coordinate the need to repair a vascular breach with the simultaneous need to induce an immune response that may limit pathogen invasion once the blood is exposed to an external environment.

Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease

“…In accordance with these experiments, the analysis of human atherosclerotic plaques revealed TLR4 overexpression in several cells types, including macrophages, vascular smooth muscle cells and dendritic cells 14,98 . However, it is unclear whether TLR4 overexpression is mediated by LPS or other TLR4 ligands, such as oxLDL, cleaved fibrinogen or heparin sulfate proteoglycan.…”

“…Other components of the TLR family are also implicated in the thrombotic process mediated by gut microbiota. For instance, TLR2 recognizes and is activated by lipoprotein components of Gram-positive or Gram-negative bacteria and has direct pro-thrombotic effects 98 . Germ-free or TLR2-deficient mice had reduced thrombus growth after carotid artery injury compared with controls, and this effect was counteracted by intestinal colonization with microbiota 120 .…”

The Neuroimmune Response to Surgery – An Exploratory Study of Trauma-Induced Changes in Innate Immunity and Heart Rate Variability

“…These observations may fuel the concern of a transition of the acute innate immune activation due to surgery onto adaptive long-term alterations within the immune system (50). The observation of a delayed thrombocytosis at 2 weeks postsurgery support these concerns (51). Finally, we cannot exclude that anesthesia per se have temporary and shortlasting influences on the regulation of immune activity, as indicated by the abrupt changes in HRV following induction and withdrawal of anesthesia (52).…”

Shining a light on platelet activation in COVID‐19

“…The dark side of this immune phenotype of platelets, however, is the collateral damage associated with systemic platelet activation. Indeed, the interplay among platelets, coagulation, and the endothelium can result in thrombotic complications, as often observed in viral and bacterial infections 13 . Likewise, it has been hypothesized that platelets contribute to thrombosis in COVID‐19 patients.…”

“…Indeed, the interplay among platelets, coagulation, and the endothelium can result in thrombotic complications, as often observed in viral and bacterial infections. 13 Likewise, it has been hypothesized that platelets contribute to thrombosis in COVID‐19 patients. Platelet‐rich thrombi were readily observed in COVID‐19 patients, 5 , 14 indicating they actively participate in COVID‐19–associated thrombosis.…”