Platelets in Infection: Intrinsic Roles and Functional Outcomes

Yuwei Hu¹Shuchang Dai¹Congchao Qiao¹Yifan Ye¹Junyi Ren²Kai Wang^3*Ling Li^4*Zhong Liu^1*

• ¹Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing Municipality, China
• ²University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China
• ³Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, China
• ⁴Chengdu Third People's Hospital, Chengdu, Sichuan Province, China

Platelets have long been acknowledged for their essential roles in hemostasis and thrombosis; however, recent insights highlight their broader involvement as key participants in host responses during infection. Beyond their classical functions, platelets exhibit diverse antiinfective capabilities, such as direct pathogen internalization, receptor-mediated pathogen recognition, the release of antimicrobial peptides, cytokines, and chemokines, and the generation of immunomodulatory extracellular vesicles. These intrinsic platelet attributes enable dynamic interactions with pathogens and immune cells, significantly contributing to pathogen capture, neutralization, and the orchestration of innate and adaptive immune responses. This review examines the multifaceted intrinsic roles of platelets and delineates the beneficial outcomes of their activation, providing an integrated perspective on platelet-driven immunity and defense mechanisms during infection.This schematic illustrates the transition of platelets from the resting to activated state and their multifaceted involvement in infection. Upon activation, platelets execute four major functions:(1) formation of immunothrombosis involving fibrin, neutrophil extracellular traps (NETs), and S. aureus to restrict pathogen spread; (2) direct interactions and internalization with various pathogens including bacteria, fungi, and viruses; (3) release of antimicrobial substances via degranulation and generation of platelet-derived microparticles (PMPs) and exosomes (PL-EXOs); and (4) modulation of immune responses through immunomodulatory factor release, chemokine secretion, and direct interaction with leukocytes. These activities are grouped into three functional roles-coagulatory, anti-infective, and immunoregulatory-ultimately contributing to pathogen sensing and capture, promotion of pathogen clearance, and modulation of immune responses.