On the Functional Overlap between Complement and Anti-Microbial Peptides.

Jana Zimmer,Cordula M Stover,Fatima Mohamed,Michael J Browning,James Hobkirk

doi:10.3389/fimmu.2014.00689

Abstract

Intriguingly, activated complement and anti-microbial peptides share certain functionalities; lytic, phagocytic, and chemo-attractant activities and each may, in addition, exert cell instructive roles. Each has been shown to have distinct LPS detoxifying activity and may play a role in the development of endotoxin tolerance. In search of the origin of complement, a functional homolog of complement C3 involved in opsonization has been identified in horseshoe crabs. Horseshoe crabs possess anti-microbial peptides able to bind to acyl chains or phosphate groups/saccharides of endotoxin, LPS. Complement activity as a whole is detectable in marine invertebrates. These are also a source of anti-microbial peptides with potential pharmaceutical applicability. Investigating the locality for the production of complement pathway proteins and their role in modulating cellular immune responses are emerging fields. The significance of local synthesis of complement components is becoming clearer from in vivo studies of parenchymatous disease involving specifically generated, complement-deficient mouse lines. Complement C3 is a central component of complement activation. Its provision by cells of the myeloid lineage varies. Their effector functions in turn are increased in the presence of anti-microbial peptides. This may point to a potentiating range of activities, which should serve the maintenance of health but may also cause disease. Because of the therapeutic implications, this review will consider closely studies dealing with complement activation and anti-microbial peptide activity in acute inflammation (e.g., dialysis-related peritonitis, appendicitis, and ischemia).

Highlights

The host defense against microorganisms relies on both innate and adaptive elements
On its own, IL-17A is a potent stimulator of anti-microbial peptide production [68], those studies reporting a deviation in complement activity, which impact on the Th17 cell population [69, 70], have to be viewed with care
We have previously reported on the complexity in design and analysis of complement-targeted mouse models [137]

Summary

Introduction

The host defense against microorganisms relies on both innate and adaptive elements. Innate immunity is the first line of defense against a microbial pathogen, which exposes a pathogenassociated molecular pattern or more a prokaryotic surface membrane, differing from eukaryotic biphospholipid layers in the complete absence of cholesterol. Locality of production plays an important role for complement proteins and for anti-microbial peptides. Complement activation products and anti-microbial peptides, which can alter their expression manifold acutely and remain altered chronically, are relevant determinants of this cell activity [65, 66].

Results

Conclusion