GP IIb/IIIa-Mediated Platelet Activation and Its Modulation of the Immune Response of Monocytes Against Candida albicans

Lin Zheng,Min Li,Zhimin Duan,Dingjie Tang,Xu Chen,Yanzhi He,Qing Chen

doi:10.3389/fcimb.2021.783085

Abstract

Candida albicans is the most common fungal pathogen in humans, causing invasive disease and even potentially life-threatening systemic infections when tissue homeostasis is disrupted. Previous studies have identified an essential role of platelets in infection and immunity, especially when they are activated. However, it is still unclear whether platelets can be activated by C. albicans, and even less is known about the role of platelets in C. albicans infection. Herein, we showed that C. albicans induced platelet activation in vitro. C. albicans elevated the levels of AKT Ser473 phosphorylation, and inhibition of the PI3K-AKT signaling pathway reversed C. albicans-induced platelet activation. Surprisingly, C. albicans-induced platelet activation occurred in an integrin glycoprotein (GP) IIb/IIIa-dependent manner but was independent of the pattern recognition receptors toll-like receptor (TLR) 2 and TLR4. Interestingly, platelets enhanced the phagocytosis of human monocytes challenged with C. albicans and upregulated the expression of inflammatory cytokines, which were dependent on platelet activation mediated by GP IIb/IIIa. The present work provides new insights into the role of activated platelets in the defense against C. albicans, highlighting the importance of GP IIb/IIIa in the recognition of C. albicans.

Highlights

Candida (C.) albicans is the most common fungal pathogen in humans, causing invasive disease and even potentially life-threatening systemic infections when tissue homeostasis is disrupted (Alby et al, 2009; Netea et al, 2015)
Several lines of evidence support a protective role for platelets in microbial infection: platelet microbicidal proteins (PMPs), kinocidins and defensins contained in platelet granules have direct antimicrobial effects (Tang et al, 2002; Yeaman, 2014); platelets and their products enhance the antimicrobial functions of immune cells by promoting phagocytosis, neutrophil extracellular trap (NET) formation and antigen presentation (Yeaman, 2014); and platelets phagocytize viruses or express the antiviral protein interferon-induced transmembrane protein 3 (IFITM3) to inhibit viral infection (Brass et al, 2009; Negrotto et al, 2015; Campbell et al, 2019)
Platelets enhance phagocytosis of human monocytes challenged with C. albicans and upregulate the expression of inflammatory cytokines, which are dependent on platelet activation mediated by GP IIb/IIIa

Summary

Introduction

Candida (C.) albicans is the most common fungal pathogen in humans, causing invasive disease and even potentially life-threatening systemic infections when tissue homeostasis is disrupted (Alby et al, 2009; Netea et al, 2015). C. albicans is an emerging multidrug-resistant fungal pathogen and generates high healthcare costs worldwide (Dadar et al, 2018). Platelets are gradually recognized to be involved in infection, inflammation and immunity, in addition to their traditional role in mediating hemostasis and thrombosis (Semple et al, 2011; Yeaman, 2014). Several lines of evidence support a protective role for platelets in microbial infection: platelet microbicidal proteins (PMPs), kinocidins and defensins contained in platelet granules have direct antimicrobial effects (Tang et al, 2002; Yeaman, 2014); platelets and their products enhance the antimicrobial functions of immune cells by promoting phagocytosis, neutrophil extracellular trap (NET) formation and antigen presentation (Yeaman, 2014); and platelets phagocytize viruses or express the antiviral protein interferon-induced transmembrane protein 3 (IFITM3) to inhibit viral infection (Brass et al, 2009; Negrotto et al, 2015; Campbell et al, 2019)

Methods

Results

Conclusion