Disease and Health Research: Recent Developments Vol. 1

Skin is the primary and largest protective organ of the human body and is colonised by a diverse community of microbiota, most of which are commensal. Under abnormal or perturbed conditions, these microbiota can behave as opportunistic pathogens. To defend against environmental threats and microbial invasion, the skin has evolved a sophisticated arsenal of factors, including antimicrobial peptides (AMPs). These AMPs not only kill pathogens directly but also modulate host immune responses to prevent infection. The canonical direct antimicrobial functions of AMPs have long been a focus in the development of enhanced therapeutics, especially against multidrug-resistant pathogens. However, more recently, the immunomodulatory functions performed by these peptides at sub-microbicidal concentrations have become a major focus in the field of host-directed therapeutics. Immunomodulation is a contemporary approach that manipulates the immune response to pathogen entry and infection. Its main goal is to enhance host-protective responses by ‘training’ immune cells to act efficiently against pathogens through the administration of modulators. Such strategies have the added benefit of reducing the likelihood that pathogens will develop resistance to immunomodulatory pathways, because pathogens exploit these signalling pathways to enter and survive within the host. Thus, this review summarises the potent immunomodulatory effects of AMPs on different host immune cells, with a view to providing an information platform that may support the design of studies to exploit and formulate effective host-directed adjunct therapeutic strategies that could act synergistically with drug regimens to counter the current diversity of drug-resistant opportunistic skin pathogens.