Host defense peptides in malaria infection: their contributions, significance and constraints

Plasmodium-induced malaria infection remains a leading global health threat. Host defense peptides (HDPs), key components of innate immunity, target multiple stages of Plasmodium development through direct antimicrobial activity and immunomodulation. These peptides represent promising agents as antimalarial compounds due to their dual role in directly targeting Plasmodium parasites and modulating host immune responses. Several HDPs, including defensins, cathelicidins, NK-2 peptide, platelet factor 4, macrophage inflammatory protein-3α, and hepcidin play pivotal roles in protecting against malaria infection. However, the roles and specific targets of HDPs in malaria defense remain incompletely understood. This review outlines the key HDPs involved in malaria defense, as well as recent findings about their specific roles towards Plasmodium parasites and infected cells. Furthermore, advancements in understanding HDP interactions with Plasmodium at various infection stages, as well as their roles in modulating the host immune response are discussed. Also, the current limitations in uncovering the full implications of HDPs in malaria infection are highlighted.