The role of cationic antimicrobial peptides in innate host defences

doi:10.1016/S0966-842X(00)01823-0

Trends in Microbiology

Volume 8, Issue 9, 1 September 2000, Pages 402-410

https://doi.org/10.1016/S0966-842X(00)01823-0 Get rights and content

Abstract

Cationic antimicrobial peptides are found in all living species. A single animal can contain >24 different antimicrobial peptides, which fall into four structural classes. These peptides are produced in large quantities at sites of infection and/or inflammation and can have broad-spectrum antibacterial, antifungal, antiviral, antiprotozoan and antisepsis properties. In addition, they interact directly with host cells to modulate the inflammatory process and innate defences.

Section snippets

Properties of cationic antimicrobial peptides

Cationic antimicrobial peptides are defined here as peptides of 12–50 amino acids with a net positive charge of +2 to +7 owing to an excess of basic amino acids (arginine, lysine and histidine) over acidic amino acids⁸. Generally speaking, 50% or more of the amino acids are hydrophobic, a fact reflected by the interaction of such peptides with bacterial membranes as part of their mechanism of action⁸. Despite their small size and common physico-chemical features, cationic antimicrobial peptides

Antimicrobial activity

Cationic antimicrobial peptides have a diverse range of targets (Table 2). The only defining characteristic of these targets is their possession of a membrane. Thus, viruses are targets for antimicrobial peptides, but only enveloped viruses such as HIV, herpesvirus and vesicular stomatitis virus (VSV). Other targets include Gram-negative and/or Gram-positive bacteria, fungi, parasites such as trypanosomes and plasmodia, and even cancer cells. Normal human cells are relatively resistant, but it

Genetics of antimicrobial peptides

Antimicrobial peptides are encoded by single genes that comprise highly homologous gene families (Fig. 1). These gene families localize to chromosomal clusters that appear to reflect the evolution of different subclasses¹¹, characterized by tissue of expression and inducibility. In humans, the defensin locus is found on chromosome 8p21–23, where both α- and β-defensins co-localize¹². The genes for α- and β- defensins maintain high sequence identity within each group, but are widely diverse from

Gene expression

It has been observed that the tissue of expression and inducibility of antimicrobial peptides reflects their gene structure. By direct sequence comparison, it was found that human enteric defensins (HD5 and -6), which are expressed in the Paneth cells of the small intestine, are encoded by two-exon genes and appear to be the evolutionary precursor of the myeloid defensins (HNP-1/3, 2 and 4)¹¹. The myeloid defensins are each encoded by three exons, and appear to be under the control of

In vivo evidence for a host defence role

The case for a primary role for antimicrobial peptides in host defences is becoming increasingly convincing. Defensins have been shown to be the most predominant protein species in neutrophils, representing nearly 15% of total protein in these dedicated anti-infective cells. Other antimicrobial peptides are found at mucosal and epithelial surfaces and in the gut, lungs, kidneys and skin. Their induction during inflammation correlates with a primary role in assisting and/or directing

Other effects of peptides on hosts

The action of cationic antimicrobial peptides is not limited to direct killing of microorganisms. Instead, they have an impressive variety of additional activities that impact particularly on the quality and effectiveness of innate immune responses and inflammation (Table 3; Fig. 3). Unfortunately, this information remains somewhat sketchy at present, as only a subset of cationic antimicrobial peptides have been examined for any given activity. Thus, in Table 3, as both natural and synthetic

Conclusions

It is becoming clear that cationic antimicrobial peptides are an important and significant component of host defences against infection. Many such peptides are encoded by mammals and are inducible under specific conditions that reflect infection, utilizing signal transduction pathways that are conserved in many eukaryotes, and are also used in induction of other innate defences. The importance of such peptides in defence against infections is attested to by experiments utilizing transgenic

Acknowledgements

The peptide research of R.H. is financially supported by the Canadian Cystic Fibrosis Foundation and the Canadian Bacterial Diseases Network. G.D. receives funding from the NIH (HL53400) and from the Cystic Fibrosis Foundation. R.H. is a Medical Research Council of Canada Distinguished Scientist.

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Trends in Microbiology

ReviewThe role of cationic antimicrobial peptides in innate host defences

Abstract

Section snippets

Properties of cationic antimicrobial peptides

Antimicrobial activity

Genetics of antimicrobial peptides

Gene expression

In vivo evidence for a host defence role

Other effects of peptides on hosts

Conclusions

Acknowledgements

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Review
The role of cationic antimicrobial peptides in innate host defences