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  • Review Article
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The immunology of host defence peptides: beyond antimicrobial activity

Nature Reviews Immunology volume 16, pages 321–334 (2016)Cite this article

Subjects

This article has been updated

Key Points

  • Host defence peptides (HDPs) display substantial immunomodulatory properties in vitro and in vivo, and these features are becoming increasingly appreciated in the literature.

  • The immune response is a highly complex process, involving multiple interconnected signalling pathways.

  • HDPs influence the entire signalling network of the immune response and, as a result, their effects on biological processes are also complex.

  • The ability of HDPs to influence many different cell types and pathways has implications in various immune-associated diseases.

  • In addition to direct antimicrobial activity and immunomodulatory activities, HDPs may have a role in biological functions such as anticancer activity, wound healing and angiogenesis.

Abstract

Host defence peptides (HDPs) are short, cationic amphipathic peptides with diverse sequences that are produced by various cells and tissues in all complex life forms. HDPs have important roles in the body's response to infection and inflammation. This Review focuses on human HDPs and explores the diverse immunomodulatory effects of HDPs from a systems biology perspective, which highlights the interconnected nature of the effect (or effects) of HDPs on the host. Studies have demonstrated that HDPs are expressed throughout the body and mediate a broad range of activities, which explains their association with various inflammatory diseases and autoimmune disorders. The diverse actions of HDPs, such as their roles in wound healing and in the maintenance of the microbiota, are also explored, in addition to potential therapeutic applications.

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Figure 1: LL-37 interacts directly and indirectly with a broad range of genes and proteins.
Figure 2: The complex response of KLA-stimulated mouse macrophages to HBD3.
Figure 3: Diversity of HDP activities within the body and relationship with disease states.

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Change history

  • 28 April 2016

    In the original version of this article, the first subheading of Table 1 was incorrect. It should read Cathelicidin LL-37. This has now been corrected online and for the print version. We apologize for this error.

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Acknowledgements

The authors' peptide research has been generously supported by the Canadian Institutes of Health Research (MOP-74493). R.E.W.H. holds a Canada Research Chair.

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Authors and Affiliations

  1. Center for Microbial Diseases Research, University of British Columbia, Vancouver, V6H 3Z6, British Columbia, Canada

    Robert E.W. Hancock, Evan F. Haney & Erin E. Gill

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  1. Robert E.W. Hancock
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  2. Evan F. Haney
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  3. Erin E. Gill
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Correspondence to Robert E.W. Hancock.

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Competing interests

R.E.W.H. is developing innate defence regulator (IDR) peptides as therapeutics and vaccine adjuvants, and has filed several patents in this area, all of which are assigned to his employer, the University of British Columbia. Two of his IDR peptides have been licensed to Elanco Animal Health Inc., for use in treatment of animals and as vaccine adjuvants, and one has been licensed to the Pan-provincial Vaccine Enterprise, for development as a component of vaccine adjuvant formulations. E.F.H. is a co-inventor on one of these patents. Recently, R.E.W.H. formed a new virtual company, ABT Innovations Inc., to promote commercialization of the University of British Columbia peptide patents. E.E.G. declares no competing interests.

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DATABASES

InnateDB

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Supplementary information

Supplementary information S1 (table)

HDP expression patterns and affected cell types and functions. (PDF 195 kb)

Glossary

Host defence peptides

(HDPs). Short (<50 amino acids) cationic amphipathic peptides with immunomodulatory and/or antimicrobial activities.

Antimicrobial peptides

Cationic peptides with an emphasis on their antimicrobial activities; traditional terminology for host defence peptides.

Immunomodulatory

The ability to modulate the immune response, including by influencing the production of chemokines and cytokines.

Innate defence regulator

(IDR). Synthetic immunomodulatory peptide derived from natural host defence peptides.

Pleiotropic

Having more than one effect on the biological system.

Diapedesis

The migration of leukocytes across the endothelium, which occurs by leukocytes squeezing through the junctions between adjacent endothelial cells.

Global transcriptional profiling

Measurement of the entire gene expression profile to obtain an overall picture of the activity of genes in a cell or biological system.

Neurotropic

Localization to nerve tissue.

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Hancock, R., Haney, E. & Gill, E. The immunology of host defence peptides: beyond antimicrobial activity. Nat Rev Immunol 16, 321–334 (2016). https://doi.org/10.1038/nri.2016.29

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