Immuno-Stimulatory Peptides as a Potential Adjunct Therapy against Intra-Macrophagic Pathogens.

Tânia Silva,Maria Gomes

doi:10.3390/molecules22081297

Abstract

The treatment of infectious diseases is increasingly prone to failure due to the rapid spread of antibiotic-resistant pathogens. Antimicrobial peptides (AMPs) are natural components of the innate immune system of most living organisms. Their capacity to kill microbes through multiple mechanisms makes the development of bacterial resistance less likely. Additionally, AMPs have important immunomodulatory effects, which critically contribute to their role in host defense. In this paper, we review the most recent evidence for the importance of AMPs in host defense against intracellular pathogens, particularly intra-macrophagic pathogens, such as mycobacteria. Cathelicidins and defensins are reviewed in more detail, due to the abundance of studies on these molecules. The cell-intrinsic as well as the systemic immune-related effects of the different AMPs are discussed. In the face of the strong potential emerging from the reviewed studies, the prospects for future use of AMPs as part of the therapeutic armamentarium against infectious diseases are presented.

Highlights

The management of infectious diseases faces an enormous challenge due to the rampant emergence of resistant and multidrug-resistant “super-bugs”
The absence of cathelicidin lead to defects on several cellular pathways such as calcium responsiveness, apoptosis and cytokine production, suggesting that increased susceptibility to infection was probably due to defects in immune signaling rather than to a reduced direct killing of the mycobacteria [31]
A different mechanism underlies the effect of the alpha defensin human neutrophil peptides (HNP)-1, which was found to decrease Listeria monocytogenes proliferation inside murine bone-marrow-derived macrophages by preventing the release and activity of listeriolysin O (LLO) [83]

Summary

Introduction

The management of infectious diseases faces an enormous challenge due to the rampant emergence of resistant and multidrug-resistant “super-bugs”. Antibiotic resistance puts at risk even the treatment of common infections. The treatment of infections is increasingly costly and prone to failure, contributing to a terrible economic burden upon public health worldwide. Aggravating the problem, antimicrobial drug development is not keeping pace with the appearance of resistant pathogens. Considering all this, we must acknowledge that we are moving towards a post-antibiotic era, where new antimicrobial strategies, including host-directed therapies, must emerge. In this context, antimicrobial peptides (AMPs) represent a new potential alternative to be considered for fighting infectious diseases.

Antimicrobial Peptides as Host Defense Peptides

Defensins and Cathelicidins as Prototypic Host Defense Peptides

The Roles of Defensins and Cathelicidins in Host Defense against Mycobacteria

Defensins and Cathelicidins in Other Intracellular Infections

Findings

Concluding Remarks