Multifunctional host defense peptides: Antimicrobial peptides, the small yet big players in innate and adaptive immunity

Abstract

The term ‘antimicrobial peptides’ refers to a large number of peptides first characterized on the basis of their antibiotic and antifungal activities. In addition to their role as endogenous antibiotics, antimicrobial peptides, also called host defense peptides, participate in multiple aspects of immunity (inflammation, wound repair, and regulation of the adaptive immune system) as well as in maintaining homeostasis. The possibility of utilizing these multifunctional molecules to effectively combat the ever‐growing group of antibiotic‐resistant pathogens has intensified research aimed at improving their antibiotic activity and therapeutic potential, without the burden of an exacerbated inflammatory response, but conserving their immunomodulatory potential. In this minireview, we focus on the contribution of small cationic antimicrobial peptides – particularly human cathelicidins and defensins – to the immune response and disease, highlighting recent advances in our understanding of the roles of these multifunctional molecules.

Immunostimulation in the era of the metagenome

“…Auvynet and Rosenstein have argued that antimicrobial peptides 'seem to participate in every facet of it [modulating immunity] by boosting the immune response to prevent infection, and also by suppressing other proinflammatory responses to avoid uncontrolled inflammation'. 29 Indeed, the activated VDR, which also increases CD14 and TLR2 synthesis, has been described as a critical regulator of the innate immune response. 30 Perversion of VDR function would clearly ease pressure on intracellular microbial communities, thus making it an obvious evolutionary selection.…”

“…31 It diminishes HIV replication and can inactivate cytomegalovirus, herpes simplex virus, vesicular stomatitis virus and adenovirus. 29 In addition to killing both gram positive and gram-negative bacteria, human beta-defensins HBD-1, HDB-2, and HBD-3 have also been shown to kill the opportunistic yeast species Candida albicans. 32 Cathelicidin also possesses antiviral and antifungal activity.…”

“…For example, mice lacking the cathelicidin gene, which is robustly transcribed by the VDR, have longer periods of wound healing than their wild-type counterparts. 29 The absence of this key AmP in a murine model might be Immunostimulation in the era of the metagenome AD Proal et al 215 compared with impaired wound healing among the elderly. 54 The term 'inflammaging' has been coined to explain 'the now widely accepted phenomenon that aging is accompanied by a low-grade chronic, systemic upregulation of the inflammatory response, and that the underlying inflammatory changes are common to most age-associated diseases'.…”

“…For example, LL-37 is generated in response to Staphylococcus aureus, yet LL-37 represents ,20% of the cathelicidin-derived peptides, with the smaller peptides being much more abundant and able to target even more diverse microbial forms. 29 Beta-defensin expression is modulated in response to bacteriaderived molecules and/or cytokines and chemokines produced by the immune system and damaged cells. For example, in immune cells, Immunostimulation in the era of the metagenome AD Proal et al 217 its production is upregulated following exposure to bacteria, lipopolysaccharides, interferon-gamma and interleukin-beta among others.…”

“…For example, in immune cells, Immunostimulation in the era of the metagenome AD Proal et al 217 its production is upregulated following exposure to bacteria, lipopolysaccharides, interferon-gamma and interleukin-beta among others. 29 So again, the beta-defensin response will differ depending on the presence and abundance of these and other factors that are, in turn, determined by the unique nature of every individual's microbiota.…”