Start a fire, kill the bug: The role of platelets in inflammation and infection

Abstract

Platelets are the main players in thrombosis and hemostasis; however they also play important roles during inflammation and infection. Through their surface receptors, platelets can directly interact with pathogens and immune cells. Platelets form complexes with neutrophils to modulate their capacities to produce reactive oxygen species or form neutrophil extracellular traps. Furthermore, they release microbicidal factors and cytokines that kill pathogens and influence the immune response, respectively. Platelets also maintain the vascular integrity during inflammation by a mechanism that is different from classical platelet activation. In this review we summarize the current knowledge about how platelets interact with the innate immune system during inflammation and infection and highlight recent advances in the field.

Keywords: Kupffer cell; Platelet; infection; inflammation; macrophages; neutrophils.

Figure 1.

Platelets interact with bacteria and cells of the innate immune system. Platelets interact with bacteria directly through their surface receptors or indirectly through plasma proteins. Platelets orchestrate the immune reaction to inflammation and infection by direct interactions with cells of the innate immune system (neutrophils and Kupffer cells) or through the secretion of mediators.

Figure 2.

Platelets form complexes with neutrophils to potentiate their activity. Platelets interact with neutrophils through multiple receptors: Activated platelets express P-Selectin on their surface which binds PSGL-1 on neutrophils and endothelial cells, CD40L is expressed on the platelet surface upon activation and binds CD40, Neutrophil Mac-1 binds platelet GPIb as well as αIIbβ3. Together these interactions promote ROS production, NET formation, adhesion, transmigration and degranulation of neutrophils. Upon activation (e.g. through PAMPS binding to TLRs), platelets release microbicidal proteins like TC1+2 which can kill bacteria. They also secrete large quantities of CXCL4 and CXCL7 that promote neutrophil adhesion, degranulation and transmigration.

Figure 3.

Platelets maintain vascular integrity during inflammation. During local inflammation (e.g. in the skin), platelet GPVI plays a dual role: On the one hand it promotes neutrophil infiltration and ROS production which causes tissue damage (a) and on the other hand it binds to the extracellular matrix protein collagen which gets exposed and facilitates platelet adhesion to restore vascular integrity (b). In the ischemic brain αIIbβ3 facilitates platelet–platelet interactions to prevent intracranial hemorrhage (c). Platelets can also bind to podoplanin, expressed on inflammatory macrophages via CLEC-2 (d). Factors secreted from platelet granules support cerebral hemostasis after stroke, for example by acting on endothelial cell receptors that stabilize cellular junctions (e).