Immunomodulatory effects of anti-microbial peptides

Abstract

Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro-and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

Synergy Between Proline-Rich Antimicrobial Peptides and Small Molecule Antibiotics Against Selected Gram-Negative Pathogens in vitro and in vivo

“…The lack of positive predictive value between in vitro microbiological activity and in vivo efficacy of the PrAMP suggests that the predominant mode of action is not direct bacterial killing; rather, the mechanism of action is likely related to the activation of host defense mechanisms (Ostorhazi et al, 2011b ). This hypothesis is supported from many prior studies of HDP and relevant infection models (Nijnik et al, 2010 ; Hilchie et al, 2013 ; Otvos, 2016 ).…”

“…Significantly, decreased doses of drugs were shown to protect mammals with modes of action different from those brought upon applying increased doses (Calabrese, 2008a ). At 5 mg/kg (in mice) the APO peptides may directly influence bacterial proliferation and at lower doses their mechanism of action may shift, possibly to an immunostimulatory function (Ostorhazi et al, 2013 ; Otvos, 2016 ). When combined with small molecule antibiotics, bacterial killing may be a consequence of the antibiotic with immune augmentation from the PrAMP.…”

Antimicrobial peptides of buffalo and their role in host defenses

“…Recently, AMPs are being referred as host defense peptides by many authors owing to the fact that these peptides act mainly through immunomodulation [ 12 ]. Immunomodulatory activities of these peptides include modulation of the production of pro-inflammatory and anti-inflammatory cytokines and chemokines, recruitment of immune cells, induction of cellular differentiation and activation, regulation of cellular processes such as autophagy, apoptosis, and pyroptosis, and also the promotion of wound healing [ 12 , 82 , 83 ]. For example, certain family members of beta-defensin have been revealed to chemoattract immature dendritic cells and CD45RO+ CD4+ T cells through chemokine receptor CCR6.…”

Antimicrobial Peptides — A Potential Replacement for Traditional Antibiotics

“…АМП могут связываться с мембранными рецепторами клеток и участвовать в иммунном ответе, начиная с воспалительных процессов и заканчивая заживлением ран [53,56].…”