Host Defence (Antimicrobial) Peptides and Proteins

Abstract Host defence (antimicrobial) peptides are small cationic peptides that contain several hydrophobic amino acids. Such peptides typically form amphipathic structures in membrane‐mimicking environments, which contribute to peptide activity on essential membrane‐dependent processes, membrane permeabilisation and/or cell penetration. Host defence peptides (HDPs) have a variety of biological properties, including profound immune‐modulating properties and direct antibacterial, antiviral, antifungal, antiparasitic and anticancer activities. Thus, HDPs are important effectors of the immune system; however, the effector functions of these peptides are often heavily dependent on their microenvironment. The direct antibacterial properties of many peptides are eliminated in the presence of physiologically relevant concentrations of cations and polyanions, although the immune‐modulating properties of these peptides persist under these conditions even in the presence of serum. The immune‐modulating properties are anti‐infective and include chemokine induction and host cell recruitment/differentiation, antiinflammatory activity, promotion of effective adaptive immunity and wound healing activity. Using human peptides as examples, the biological properties of HDPs are discussed herein in an attempt to expose their potential as templates for novel therapeutic agents. Key Concepts: The direct antimicrobial properties of small cationic peptides are often eliminated in the presence of physiologically relevant concentrations of serum and salt; thus they are more accurately described as host defence peptides. The immunomodulatory properties of host defence peptides are complex, have been confirmed in vivo , and contribute to anti‐infective immunity. Humans express several defensins and one cathelicidin (hCAP‐18/LL‐37). Human defensins and cathelicidins are produced by many cell types and have many biological properties, including the ability to destroy pathogens and alter immune responses. Host defence peptides can be modified to improve their biological activities.