Crosstalk Between Platelets and Microbial Pathogens

Abstract

Platelets, small anucleate cells circulating in the blood, are critical mediators in haemostasis and thrombosis. Interestingly, recent studies demonstrated that platelets contain both pro-inflammatory and anti-inflammatory molecules, equipping platelets with immunoregulatory function in both innate and adaptive immunity. In the context of infectious diseases, platelets are involved in early detection of invading microorganisms and are actively recruited to sites of infection. Platelets exert their effects on microbial pathogens either by direct binding to eliminate or restrict dissemination, or by shaping the subsequent host immune response. Reciprocally, many invading microbial pathogens can directly or indirectly target host platelets, altering platelet count or/and function. In addition, microbial pathogens can impact the host auto- and alloimmune responses to platelet antigens in several immune-mediated diseases, such as immune thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. In this review, we discuss the mechanisms that contribute to the bidirectional interactions between platelets and various microbial pathogens, and how these interactions hold relevant implications in the pathogenesis of many infectious diseases. The knowledge obtained from "well-studied" microbes may also help us understand the pathogenesis of emerging microbes, such as SARS-CoV-2 coronavirus.

Keywords: COVID-19; host immune responses; microbial pathogens; platelets; thrombosis.

Figure 1

Bidirectional interaction between platelets and microbial pathogens. Microbes encounter platelets when they enter the mammalian blood circulation. Platelets exert their direct effects on microbial pathogens by either binding them and sequestering them thereby limiting their systemic dissemination or by directly eliminating them, and indirect effects by shaping the subsequent host immune response to these invaders. Reciprocally, many invading microbes can alter platelet count or/and function, and impact the host auto- and alloimmune response to platelet antigens in several immune-mediated diseases.

Figure 2

Effects of platelets on microbial pathogens. The direct effects of platelets on microbial pathogens include pathogen encapsulation and elimination. Platelets also exert the indirect effects on microbial pathogens by shaping the innate and adaptive immune responses of the host against these invaders.

Figure 3

Effects of microbial pathogens on platelets. Many invading microbes can alter platelet function, leading to platelet activation or/and apoptosis. Reduced platelet count is a common feature with some infectious diseases, and the underlying mechanisms include accelerated platelet clearance and impaired platelet production. In addition, microbial pathogens impact the host autoimmune (e.g., in ITP) and alloimmune (e.g., in FNAIT) response to platelet antigens. VZV, varicella zoster virus.