Platelets as Immune Cells in Infectious Diseases

Cornelia Speth; Jürgen Löffler; Sven Krappmann; Cornelia Lass-Flörl; Günter Rambach

Disclosures

Future Microbiol. 2013;8(11):1431-1451. 

In This Article

Abstract and Introduction

Abstract

Platelets have been shown to cover a broad range of functions. Besides their role in hemostasis, they have immunological functions and thus participate in the interaction between pathogens and host defense. Platelets have a broad repertoire of receptor molecules that enable them to sense invading pathogens and infection-induced inflammation. Consequently, platelets exert antimicrobial effector mechanisms, but also initiate an intense crosstalk with other arms of the innate and adaptive immunity, including neutrophils, monocytes/macrophages, dendritic cells, B cells and T cells. There is a fragile balance between beneficial antimicrobial effects and detrimental reactions that contribute to the pathogenesis, and many pathogens have developed mechanisms to influence these two outcomes. This review aims to highlight aspects of the interaction strategies between platelets and pathogenic bacteria, viruses, fungi and parasites, in addition to the subsequent networking between platelets and other immune cells, and the relevance of these processes for the pathogenesis of infections.

Introduction

Platelets, are small cell fragments in the circulating blood. Their primary role includes sensing of damaged blood vessel endothelium, accumulating at the site of injury and then causing blood clotting to close the wound.[1] In addition, they are part of the innate and adaptive immune system, play a role in the initiation of inflammation by interacting with leukocytes, and are further involved in atherosclerosis and tumor growth.[1–3]

Platelets originate from megakaryocytes, which are precursor cells in the bone marrow that develop from pluripotent stem cells by a multistep process.[4–7]

With an irregular size of 2.0–5.0 µm in diameter, the 150–400 × 109 platelets per liter of human blood have a life span of 8–10 days.[1] Despite lacking a nucleus, platelets contain mRNA and the full translation machinery for protein synthesis.[1] The discoid shape in their resting stage is stabilized by a membrane skeleton, microtubules and microfilaments.[8] Periodic invaginations punctuate the even-textured surface to an open canalicular system that permeates the cytoplasm resulting in a large surface area for protein uptake.[9] Most of those proteins are stored in secretory vesicles called granules, which can be divided into lysosomal granules, dense bodies and α-granules.

Per platelet, three to eight dense bodies contain molecules involved in platelet activation and aggregation such as nucleotides, cations, phosphates and bioactive amines such as serotonin.[10,11] Lysosomal granules store enzymes such as proteases, phosphatases and glycosidases, which are responsible for matrix and protein degradation.[10] With 40–80 per platelet, α-granules are the most abundant secretory vesicles and they contain over 300 soluble and membrane-bound molecules including microbicidal peptides, growth factors, soluble adhesion molecules and coagulation proteins.[10,12,13] Additionally, proinflammatory molecules, such as cytokines, chemokines and interleukins, are stored in α-granules.[11]

Intact vessel endothelial cells suppress platelet activation.[14] In case of vessel injury, platelets adhere to and become activated by the subendothelial collagen–von Willebrand factor (vWF) complex and thrombin. Hereon, a shape change from smooth disks to spiculated spheres with filopodia and pseudopodia is performed by actin reorganization.[8,15] Thereby, the cargo of the granules becomes released in the surrounding bloodstream and recruits and activates further platelets.[16] In addition, membrane-bound molecules, for example, P-selectin become translocated to the platelet surface, promoting platelet aggregation and interaction with immune and endothelial cells.[17] The chemokines and interleukins stored in α-granules link platelets to antimicrobial host defense and inflammation.[11,18] Furthermore, platelets generate microparticles[19] with P-selectin, glyoproteins (GPs) and CD154 on their surface.[20,21]

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