Platelets and the innate immune system: mechanisms of bacterial‐induced platelet activation

Abstract

Summary. It has become clear that platelets are not simply cell fragments that plug the leak in a damaged blood vessel; they are, in fact, also key components in the innate immune system, which is supported by the presence of Toll‐like receptors (TLRs) on platelets. As the cells that respond first to a site of injury, they are well placed to direct the immune response to deal with any resulting exposure to pathogens. The response is triggered by bacteria binding to platelets, which usually triggers platelet activation and the secretion of antimicrobial peptides. The main platelet receptors that mediate these interactions are glycoprotein (GP)IIb–IIIa, GPIbα, FcγRIIa, complement receptors, and TLRs. This process may involve direct interactions between bacterial proteins and the receptors, or can be mediated by plasma proteins such as fibrinogen, von Willebrand factor, complement, and IgG. Here, we review the variety of interactions between platelets and bacteria, and look at the potential for inhibiting these interactions in diseases such as infective endocarditis and sepsis.

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

“…Within the last 15 years it became more and more evident that nonnucleated platelets are also implicated in the adaptive [2] as well as being components of the innate immune system [3,4], the latter which came into focus by the discovery that platelets express Toll-like receptors (TLRs) [5], of which TLR4, TLR2, and TLR9 were found to be the most abundant [6,7]. TLR2, in particular, forms heterodimers with TLR1 or TLR6, which is the prerequisite to recognize a wide spectrum of microbial pathogen-associated molecules such as peptidoglycans and lipopeptides [8,9].…”

Modulation of the immuno-coagulative response in a pneumococcal infection in malnourished mice nasally treated with Lactobacillus casei

“…However, they can have an early role in immune surveillance and in the transfer of pathogen information to other innate immune cells. These functions are supported by the presence of TLRs on platelets (Alves-Filho, 2005;Cox et al, 2011). Also, platelets may play an important role in pathogen clearance and are involved in leukocyte function.…”

Platelets in sepsis — are there any new aspects?

“…This process promotes platelet adhesion with the endothelium, other platelets and leucocytes, leading to the formation and release of inflammatory and thrombotic agents, further leucocyte recruitment, oedema formation [28]. It has been shown that, LPS leads to enhanced formation of neutrophil-platelet complexes, resulting in the formation of neutrophil extracellular traps (NETs), a key mechanism used by innate immune cells in immunothrombosis [4,7] (Fig. 2).…”

“…Although it can bind several different ligands, its crucial role in primary haemostasis relies on its ability to interact with von Willebrand factor (VWF). GPIbα exists in a complex with GPIbβ,GPIX and GPV in a ratio of 2:2:2:1 [7].…”