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.
At a glance
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This review summarizes many of the immunomodulatory roles of HDPs, with a specific emphasis on animal studies.
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This review provides a thorough summary of the structure, expression and diverse activities of LL-37.
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This article describes a systems analysis of CD14+ monocytes that are exposed to LL-37 and outlines the various genes and pathways that respond to this stimulus; in particular, MAPK signalling proteins and their targets are investigated.
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This review outlines the structures, expression patterns and biological activities of defensins.
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This article describes the response of mouse macrophages to HBD3 in combination with TLR4 stimuli. The specific pathways that are modulated by this HDP to achieve its anti-inflammatory effects are outlined.
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- Synthetic cationic peptide IDR- 1018 modulates human macrophage differentiation. PLoS ONE 8, e52449 (2013).
This paper describes the effects of a synthetic HDP, IDR-1018, on macrophage differentiation; macrophages stimulated with IDR-1018 display a phenotype in-between the classical M1 and M2 states.
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- Functional synergism of Human Defensin 5 and Human Defensin 6. Biochem. Biophys. Res. Commun. 467, 967–972 (2015).
This paper describes one of the first examples of immunomodulatory synergy between two natural HDPs.
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- Association studies of the copy-number variable ß-defensin cluster on 8p23.1 in adenocarcinoma and chronic pancreatitis. BMC Res. Notes 5, 629 (2012). et al.
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- Treatment with LL-37 peptide enhances antitumor effects induced by CpG oligodeoxynucleotides against ovarian cancer. Hum. Gene Ther. 20, 303–313 (2009). , , , &
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- From antimicrobial to anticancer peptides. A review. Front. Microbiol. 4, 294 (2013).
This review summarizes the relationship between HDPs and anticancer peptides.
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- Broad-spectrum anti-biofilm peptide that targets a cellular stress response. PLoS Pathog. 10, e1004152 (2014).
This paper details the mechanism of antibiofilm activity for a synthetic HDP.
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- 1,25-dihydroxyvitamin D3 induces LL-37 and HBD-2 production in keratinocytes from diabetic foot ulcers promoting wound healing: an in vitro model. PLoS ONE 9, e111355 (2014). et al.
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- The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J. Invest. Dermatol. 120, 379–389 (2003). et al.
- Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure. Am. J. Physiol. Lung Cell. Mol. Physiol. 289, L842–L848 (2005). et al.
- Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J. Immunol. 175, 4662–4668 (2005). et al.
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- Antimicrobial peptide, lumbricusin, ameliorates motor dysfunction and dopaminergic neurodegeneration in a mouse model of parkinson's disease. J. Microbiol. Biotechnol. 25, 1640–1647 (2015). et al.
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- Copy number variation of the β defensin gene cluster on chromosome 8p influences the bacterial microbiota within the nasopharynx of otitis-prone children. PLoS ONE 9, e98269 (2014). , , , &
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- Supplementary information S1 (table) (195 KB)
HDP expression patterns and affected cell types and functions.