Platelets can be considered sentinels of vascular system due to their high number in the circulation and to the range of functional immunoreceptors they express. Platelets express a wide range of potential bacterial receptors, including complement receptors, FcγRII, Toll-like receptors but also integrins conventionally described in the hemostatic response, such as GPIIb–IIIa or GPIb. Bacteria bind these receptors either directly, or indirectly via fibrinogen, fibronectin, the first complement C1q, the von Willebrand Factor, etc. The fate of platelet-bound bacteria is questioned. Several studies reported the ability of activated platelets to internalize bacteria such as Staphylococcus aureus or Porphyromonas gingivalis, though there is no clue on what happens thereafter. Are they sheltered from the immune system in the cytoplasm of platelets or are they lysed? Indeed, while the presence of phagolysosome has not been demonstrated in platelets, they contain antimicrobial peptides that were shown to be efficient on S. aureus. Besides, the fact that bacteria can bind to platelets via receptors involved in hemostasis suggests that they may induce aggregation; this has indeed been described for Streptococcus sanguinis, S. epidermidis, or C. pneumoniae. On the other hand, platelets are able to display an inflammatory response to an infectious triggering. We, and others, have shown that platelet release soluble immunomodulatory factors upon stimulation by bacterial components. Moreover, interactions between bacteria and platelets are not limited to only these two partners. Indeed, platelets are also essential for the formation of neutrophil extracellular traps by neutrophils, resulting in bacterial clearance by trapping bacteria and concentrating antibacterial factors but in enhancing thrombosis. In conclusion, the platelet–bacteria interplay is a complex game; its fine analysis is complicated by the fact that the inflammatory component adds to the aggregation response.

Platelets are non-nucleated cells that play central roles in the processes of hemostasis, innate immunity, and inflammation; however, several reports show that these distinct functions are more closely linked than initially thought. Platelets express numerous receptors and contain hundreds of secretory products. These receptors and secretory products are instrumental to the platelet functional responses. The capacity of platelets to secrete copious amounts of cytokines, chemokines, and related molecules appears intimately related to the role of the platelet in inflammation. Platelets exhibit non-self-infectious danger detection molecules on their surfaces, including those belonging to the “toll-like receptor” family, as well as pathogen sensors of other natures (Ig- or complement receptors, etc.). These receptors permit platelets to both bind infectious agents and deliver differential signals leading to the secretion of cytokines/chemokines, under the control of specific intracellular regulatory pathways. In contrast, dysfunctional receptors or dysregulation of the intracellular pathway may increase the susceptibility to pathological inflammation. Physiological vs. pathological inflammation is tightly controlled by the sensors of danger expressed in resting, as well as in activated, platelets. These sensors, referred to as pathogen recognition receptors, primarily sense danger signals termed pathogen associated molecular patterns. As platelets are found in inflamed tissues and are involved in auto-immune disorders, it is possible that they can also be stimulated by internal pathogens. In such cases, platelets can also sense danger signals using damage associated molecular patterns (DAMPs). Some of the most significant DAMP family members are the alarmins, to which the Siglec family of molecules belongs. This review examines the role of platelets in anti-infection immunity via their TLRs and Siglec receptors.

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This study demonstrates the putative participation of PLT-derived sOX40L, IL-27, and sCD40L, which accumulate in PC supernatants, with inflammatory-type ATRs. Further studies are required to determine the clinical significance of these findings to forecast preventive measures whenever possible.

Toll-like receptor 4 signal transduction in platelets: novel pathwaysIn addition to their roles in haemostasis and thrombosis, platelets are important players in several other processes and their role in inflammation is also recognized (Weyrich & Zimmerman, 2004). Platelets express transcription factors involved in non-genomic functions, including the positive and negative regulation of platelet activation. Recent studies (Malaver et al, 2009; Spinelli et al, 2010) have proposed that inhibition of platelet nuclear factor jB (NFjB) leads to the modulation of platelet function and that NFjB may be a novel mediator of platelet response. NFjB is the major transcription factor that regulates the genes involved in immune responses. In addition to membrane expression of TLRs, platelets also contain molecules with known immunomodulatory competences, and these molecules may either be accumulated mostly or released upon signalling and, depending on the nature of the molecule and prevailing environmental conditions.Studies by our group and others have furnished evidence of a functional role for TLR2 and 4 on platelets (Clark et al, 2007;Blair et al, 2008;Cognasse et al, 2008). However, the intracellular signalling pathways that mediate TLR2-and TLR4-induced platelet activation have not been investigated in detail. The aim of this study was to examine the platelet TLR4 machinery pathway.Peripheral blood was collected from healthy donors in endotoxin-free 3AE2% sodium citrate tubes (Vacutainer Ò , Becton-Dickinson, San Jose, CA, USA). Platelet-rich plasma (PRP) was prepared by centrifuging the blood at 150 g for 12 min at room temperature. Contamination (CD3-T cells, CD19-B cells and CD14-monocytes), determined by flow cytometry, was undetectable in PRP (data not shown). Peripheral blood mononuclear cells (PBMCs) were prepared as described previously , and cell lysates were prepared for use as positive controls in the Western blotting assay. Platelet protein extract (1 lg) was loaded in each well and separated on a 10% acrylamide gel (Sigma-Aldrich, Saint Quentin Fallavier, France). The gel was then transferred onto a 0AE45-lm nitrocellulose membrane (Amersham Pharmacia, Orsay, France) by electroblotting using transfer buffer supplemented with 20% methanol (Sigma-Aldrich). The blots were blocked overnight at 4°C in phosphate-buffered saline containing 0AE1% Tween 20 and 1% bovine serum albumin (I.D. Bio, Limoges, France). These were then incubated for 60 min at room temperature with the primary antibody against TLR4 (1/500; Imgenex, San Diego, CA, USA) and TLR4 signalling pathway molecules as described in Table I. A histone H3 antibody (diluted 1/1000; Abcam, Cambridge, MA, USA) was used as the negative control for the platelet protein extract. The blots were washed three times for 10 min with blocking buffer and again incubated for 60 min with the secondary antibody (horseradish peroxidase-linked goat anti-rabbit or anti-mouse antibody, diluted 1/100 000; Santa Cruz Biotechnology, Santa Cruz, CA, USA). Next, the blots wer...