The role of cathelicidins in neutrophil biology

Despite their relatively short lifespan, neutrophils are tasked with counteracting pathogens through various functions, including phagocytosis, production of reactive oxygen species, neutrophil extracellular traps (NETs), and host defense peptides. Regarding the latter, small cationic cathelicidins present a conundrum in neutrophil function. Although primarily recognized as microbicides with an ability to provoke pores in microbial cell walls, the ability of cathelicidin to modulate key neutrophil functions is also of great importance, including the release of chemoattractants, cytokines, and reactive oxygen species, plus prolonging neutrophil lifespan. Cumulative evidence indicates a less recognized role of cathelicidin as an "immunomodulator"; however, this term is not always explicit, and its relevance in neutrophil responses during infection and inflammation is seldom discussed. This review compiles and discusses studies of how neutrophils use cathelicidin to respond to infections, while also acknowledging immunomodulatory aspects of cathelicidin through potential crosstalk between sources of the peptide.