Focusing on the role of platelets in immune defence against invading pathogens

This series of reviews focuses on the rapidly emerging area of platelet–bacterial interaction. The primary function of platelets is adhesion to exposed matrix protein components at sites of trauma in order to allow haemostasis and initiate wound repair [1]. As our knowledge of basic platelet biology is developing, there is a greater appreciation that platelets are powerful multifunctional cells involved in a large number of processes beyond their traditional role in thrombosis and haemostasis. An area making significant progress at the moment is the role platelets play in host defence. Although professional leukocytes are well characterised for their role in immuno-protection following invasion by microbes, current data suggest platelets can also respond to foreign invaders and in doing so may orchestrate the immune response.

For example, upon engagement of the foreign invader, platelets become activated and release their granule contents, which include a number of key immune regulators. Platelet alpha granules contain proteins such as P-selectin which mediates adhesion of platelets to monocytes, neutrophils and lymphocytes, resulting in the formation of platelet–leukocyte complexes. Secretion also results in the release of many chemotactic agents which lead to the recruitment of various inflammatory cells: platelet-derived growth factor (PDGF) and 12-hydroxyeicosatetraenoic acid (12-HETE) recruit neutrophils; platelet factor 4 (PF4) and platelet-derived histamine releasing factor (PDHRF) recruit eosinophils in airway disease; PDGF and transforming growth factor β (TGF-β) recruit monocytes and macrophages and TGF-β recruits fibroblasts. In addition, alpha granules release many antimicrobial peptides such as beta-lysin, platelet microbicidal protein (PMP), neutrophil activating peptide (NAP-2), Released upon Activation Normal T-cell Expressed and Secreted (RANTES) and fibrinopeptides A and B [2].

In order to orchestrate the immune response efficiently, platelets express a number of receptors critical for recruiting the professional immune cells. These include Intracellular Cell Adhesion Molecular (ICAM) 2 which binds to leukocyte β2 integrin; LFA-1 (α1β2, CD11a/CD18) and to dendritic cell specific ICAM grabbing nonintegrin (DC-SIGN). Trans-interactions of platelet-derived junctional adhesion molecules (JAM-A and JAM-C) have been found to support the luminal deposition of platelet chemokines and to enhance the recruitment of leukocytes. Upon activation, CD40L is upregulated on the platelet surface which results in stimulation of endothelial cells through its cognate receptor CD40 and in increased expression of adhesion molecules, release of chemokines (e.g. RANTES) enhancing recruitment of leukocytes [3]. Given the functional make-up of platelets there is little doubt that they are perfectly suited to direct and respond to immune processes.

Of all the foreign invaders that can interact with platelets, bacteria pose the biggest threat. This series of reviews will focus on current evidence linking haemostasis to host defence. The first review by Jenne and Kubes focuses on platelets as immune sentinels and as primary responders to infection. Following recognition, bacteria use two mechanisms to engage with or activate platelets. The first reviewed by Kerrigan is a direct physical interaction, where specific bacterial proteins interact with specific platelet receptors to mediate tethering, firm adhesion, spreading, aggregation and/or thrombus formation. In the second mechanism reviewed by Shannon, bacteria secrete a variety of proteins or toxins that engage with platelet receptors leading to either cell lysis, activation or aggregation. These form the basis of the next two articles in the series. The link between these two mechanisms of platelet–bacteria interaction is the signalling pathways that are activated in platelets by bacteria, and this is the focus of the fourth article in this set which is reviewed by McNicol. As the field of platelet–bacterial interaction develops there is a growing interest in other foreign invaders and how they interact with platelets. The final review in this series by Lopez and Cox will focus on these emerging interactions.

Declaration of interest

The authors report no conflicts of interest.