Host Defence (Antimicrobial) Peptides and Proteins


Host defence (antimicrobial) peptides are small cationic peptides that contain several hydrophobic amino acids. Such peptides typically form amphipathic structures in membrane‐mimicking environments, which contribute to peptide activity on essential membrane‐dependent processes, membrane permeabilisation and/or cell penetration. Host defence peptides (HDPs) have a variety of biological properties, including profound immune‐modulating properties and direct antibacterial, antiviral, antifungal, antiparasitic and anticancer activities. Thus, HDPs are important effectors of the immune system; however, the effector functions of these peptides are often heavily dependent on their microenvironment. The direct antibacterial properties of many peptides are eliminated in the presence of physiologically relevant concentrations of cations and polyanions, although the immune‐modulating properties of these peptides persist under these conditions even in the presence of serum. The immune‐modulating properties are anti‐infective and include chemokine induction and host cell recruitment/differentiation, antiinflammatory activity, promotion of effective adaptive immunity and wound healing activity. Using human peptides as examples, the biological properties of HDPs are discussed herein in an attempt to expose their potential as templates for novel therapeutic agents.

Key Concepts:

  • The direct antimicrobial properties of small cationic peptides are often eliminated in the presence of physiologically relevant concentrations of serum and salt; thus they are more accurately described as host defence peptides.

  • The immunomodulatory properties of host defence peptides are complex, have been confirmed in vivo, and contribute to anti‐infective immunity.

  • Humans express several defensins and one cathelicidin (hCAP‐18/LL‐37).

  • Human defensins and cathelicidins are produced by many cell types and have many biological properties, including the ability to destroy pathogens and alter immune responses.

  • Host defence peptides can be modified to improve their biological activities.

Keywords: host defence peptides; immunomodulatory; innate immunity; antimicrobial peptides; anti‐infective

Figure 1.

Overview of the properties of cationic host defence peptides. In an immune response to infection (microbes denoted by small open circles: ○), host defence peptides engage in interaction with cells of the innate immune system to stimulate multiple mechanisms of anti‐infective immunity as well as direct microbial killing at higher concentrations. Reprinted from Brown and Hancock .

Figure 2.

Bacterial targets of selected host defence peptides and proteins. Direct antimicrobial activity occurs primarily in phagocytic granules and intestinal crypts where there is a high concentration of defence peptides and proteins. Antimicrobial activity is generally directed at critical membrane‐associated processes (e.g. cell wall synthesis and cell division), microbial membrane integrity and intracellular molecules critical to growth and maintenance (in bold).

Figure 3.

Models of HDP‐mediated membrane disruption. In the carpet model, HDPs cover the surface of the target cell like a carpet, which results in significant phospholipid displacement. Upon reaching a threshold concentration, transient pores lined with HDPs are formed. The barrel‐stave model suggests that HDP binding to the surface of the target cell results in peptide aggregation whereby the peptides begin to insert themselves deeper into the membrane, causing the formation of transmembrane pores composed solely of peptides. In contrast, the toroidal pore model suggests that membrane pores are torus‐shaped and composed of HDPs and lipids. Finally, in the aggregate model, transient pores that lack a defined structure are composed of peptides aggregated with membrane lipids. The aggregate model can also explain translocation across the cytoplasmic membrane to access intracellular targets due to the resolution of the aggregate leading to peptide access to the cytoplasm.



Aarbiou J, Tjabringa GS, Verhoosel RM et al. (2006) Mechanisms of cell death induced by the neutrophil antimicrobial peptides alpha‐defensins and LL‐37. Inflammation Research 55: 119–127.

Adlerova L, Bartoskova A and Faldyna M (2008) Lactoferrin: a review. Veterinarni Medicina 53: 457–468.

Afacan NJ, Yeung AT, Pena OM and Hancock RE (2012) Therapeutic potential of host defense peptides in antibiotic‐resistant infections. Current Pharmaceutical Design 18: 807–819.

Agerberth B, Charo J, Werr J et al. (2000) The human antimicrobial and chemotactic peptides LL‐37 and alpha‐defensins are expressed by specific lymphocyte and monocyte populations. Blood 96: 3086–3093.

Amulic B, Cazalet C, Hayes GL, Metzler KD and Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annual Review of Immunology 30: 459–489.

Antcheva N, Guida F and Tossi A (2013) The Defensins. In: Kastin AJ (ed.) Handbook of Biologically Active Peptides, pp. 101–118. Burlington, MA: Elsevier.

Ayabe T, Satchell DP, Wilson CL et al. (2000) Secretion of microbicidal alpha‐defensins by intestinal Paneth cells in response to bacteria. Nature Immunology 1: 113–118.

Bang C, Schilhabel A, Weidenbach K et al. (2012) Effects of antimicrobial peptides on methanogenic archaea. Antimicrobial Agents and Chemotherapy 56: 4123–4130.

Barlow PG, Li Y, Wilkinson TS et al. (2006) The human cationic host defense peptide LL‐37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. Journal of Leukocyte Biology 80: 509–520.

Barlow PG, Svoboda P, Mackellar A et al. (2011) Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL‐37. PLoS One 6: e25333.

Berge G, Eliassen LT, Camilio KA et al. (2010) Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide. Cancer Immunology, Immunotherapy 59: 1285–1294.

Bergman P, Walter‐Jallow L, Broliden K, Agerberth B and Soderlund J (2007) The antimicrobial peptide LL‐37 inhibits HIV‐1 replication. Current HIV Research 5: 410–415.

Biragyn A, Ruffini PA, Leifer CA et al. (2002) Toll‐like receptor 4‐dependent activation of dendritic cells by beta‐defensin 2. Science 298: 1025–1029.

Bowdish DME, Davidson DJ, Lau YE et al. (2005) Impact of LL‐37 on anti‐infective immunity. Journal of Leukocyte Biology 77: 451–459.

Brown KL and Hancock REW (2006) Cationic host defence (antimicrobial). Current Opinion in Immunology 18: 24–30.

Chaly YV, Paleolog EM, Kolesnikova TS et al. (2000) Neutrophil alpha‐defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. European Cytokine Network 11: 257–266.

Coffelt SB and Scandurro AB (2008) Tumors sound the alarmin(s). Cancer Research 68: 6482–6485.

Crack LR, Jones L, Malavige GN, Patel V and Ogg GS (2012) Human antimicrobial peptides LL‐37 and human beta‐defensin‐2 reduce viral replication in keratinocytes infected with varicella zoster virus. Clinical and Experimental Dermatology 37: 534–543.

Davidson DJ, Currie AJ, Reid GS et al. (2004) The cationic antimicrobial peptide LL‐37 modulates dendritic cell differentiation and dendritic cell‐induced T cell polarization. Journal of Immunology 172: 1146–1156.

Eckert R (2011) Road to clinical efficacy: challenges and novel strategies for antimicrobial peptide development. Future Microbiology 6: 635–651.

Fjell CD, Hiss JA, Hancock REW and Schneider G (2012) Designing antimicrobial peptides: form follows function. Nature Reviews Drug Discovery 11: 37–51.

Fujita T, Matsushita M and Endo Y (2004) The lectin‐complement pathway – its role in innate immunity and evolution. Immunological Reviews 198: 185–202.

Funderburg N, Lederman MM, Feng Z et al. (2007) Human ‐defensin‐3 activates professional antigen‐presenting cells via Toll‐like receptors 1 and 2. Proceedings of the National Academy of Sciences of the USA 104: 18631–18635.

Ganz T (2001) Antimicrobial proteins and peptides in host defense. Seminars in Respiratory Infections 16: 4–10.

Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nature Reviews Immunology 3: 710–720.

Ganz T (2004) Antimicrobial polypeptides. Journal of Leukocyte Biology 75: 34–38.

Gennaro R and Zanetti M (2000) Structural features and biological activities of the cathelicidin‐derived antimicrobial peptides. Biopolymers 55: 31–49.

Gong J, Nicholls EF, Elliot MR et al. (2010) G‐protein‐coupled receptor independent, immunomodulatory properties of chemokine CXCL9. Cellular Immunology 261: 105–113.

Guermonprez P, Valladeau J, Zitvogel L, Thery C and Amigorena S (2002) Antigen presentation and T cell stimulation by dendritic cells. Annual Review of Immunology 20: 621–667.

Guo CJ, Tan N, Song L, Douglas SD and Ho WZ (2004) Alpha‐defensins inhibit HIV infection of macrophages through upregulation of CC‐chemokines. AIDS 18: 1217–1218.

Hancock REW, Nijnik A and Philpott DJ (2012) Modulating immunity as a therapy for bacterial infections. Nature Reviews Microbiology 10: 243–254.

Harder J, Bartels J, Christophers E and Schroder JM (1997) A peptide antibiotic from human skin. Nature 387: 861.

Hilchie AL and Hoskin D (2010) Application of cationic antimicrobial peptides in cancer treatment: laboratory investigations and clinical potential. In: Fialho AM and Chakrabarty AM (eds) Emerging Cancer Therapy: Microbial Approaches and Biotechnological Tools, pp. 309–332. New Jersey: John Wiley & Sons, Inc.

Hilchie AL, Doucette C, Pinto D et al. (2011) Pleurocidin‐family cationic antimicrobial peptides are cytolytic for human breast carcinoma cells and prevent tumour xenograft growth. Breast Cancer Research 13: R102.

Jenssen H, Hamill P and Hancock REW (2006) Peptide antimicrobial agents. Clinical Microbiology Reviews 19: 491–511.

Korkmaz B, Horwitz MS, Jenne DE and Gauthier F (2010) Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacological Reviews 62: 726–759.

Lai Y and Gallo RL (2009) AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends in Immunology 30: 131–141.

Lillard JW Jr, Boyaka PN, Chertov O, Oppenheim JJ and McGhee JR (1999) Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proceedings of the National Academy of Sciences of the USA 96: 651–656.

Lynn MA, Kindrachuk J, Marr AK et al. (2011) Effect of BMAP‐28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. PLoS Neglected Tropical Diseases 5: e1141.

Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449: 819–826.

Mookerhjee N, Brown KL and Hancock REW (2013) Cathelicidins (chapter 15). In: Kastin AJ (ed.) Handbook of Biologically Active Peptides, pp. 77–84. Burlington, MA: Elsevier.

Nijnik A and Hancock R (2009) Host defence peptides: antimicrobial and immunomodulatory activity and potential applications for tackling antibiotic‐resistant infections. Emerging Health Threats Journal 2: e1.

Rehaume L and Hancock REW (2008) Neutrophil‐derived defensins as modulators of innate immune function. Critical Reviews in Immunology 28: 185–200.

Riley MA and Wertz JE (2002) Bacteriocins: evolution, ecology, and application. Annual Review of Microbiology 56: 117–137.

de Saint Basile G, Menasche G and Fischer A (2010) Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules. Nature Reviews Immunology 10: 568–579.

Seidel A, Ye Y, de Armas LR et al. (2010) Cyclic and acyclic defensins inhibit human immunodeficiency virus type‐1 replication by different mechanisms. PLoS One 5: e9737.

Shard RF and Leyva KJ (2008) Archaeal antimicrobials: an undiscovered country. In: Blum P (ed.) Archaea: New models for Prokaryotic Biology, pp. 233–243. Norfolk, UK: Caister Academic Press.

Sorensen OE, Follin P, Johnsen AH et al. (2001) Human cathelicidin, hCAP‐18, is processed to the antimicrobial peptide LL‐37 by extracellular cleavage with proteinase 3. Blood 97: 3951–3959.

Sorensen OE, Gram L, Johnsen AH et al. (2003) Processing of seminal plasma hCAP‐18 to ALL‐38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. Journal of Biologial Chemistry 278: 28540–28546.

Territo MC, Ganz T, Selsted ME and Lehrer R (1989) Monocyte‐chemotactic activity of defensins from human neutrophils. Journal of Clinical Investigation 84: 2017–2020.

Wang W, Owen SM, Rudolph DL et al. (2004) Activity of alpha‐ and theta‐defensins against primary isolates of HIV‐1. Journal of Immunology 173: 515–520.

Yang YH, Zheng GG, Li G et al. (2003) Expression of LL‐37/hCAP‐18 gene in human leukemia cells. Leukemia Research 27: 947–950.

Yasin B, Pang M, Turner JS et al. (2000) Evaluation of the inactivation of infectious Herpes simplex virus by host‐defense peptides. European Journal of Clinical Microbiology & Infectious Diseases 19: 187–194.

Yeung ATY, Gellatly SL and Hancock REW (2011) Multifunctional cationic host defence peptides and their clinical applications. Cellular and Molecular Life Sciences 68: 2161–2176.

Zhang H, Porro G, Orzech N et al. (2001) Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose‐related fashion. American Journal of Physiology – Lung Cellular and Molecular Physiology 280: L947–L954.

Further Reading

Bowdish DME, Davidson DJ and Hancock REW (2005) A re‐evaluation of the role of host defence peptides in mammalian immunity. Current Protein and Peptide Science 6: 35–51.

Coffelt SB and Scandurro AB (2008) Tumors sound the alarmin(s). Cancer Research 68: 6482–6485.

Hancock REW and Sahl HG (2006) Antimicrobial and host‐defence peptides as novel anti‐infective therapeutic strategies. Nature Biotechnology 24: 1551–1557.

Oppenheim JJ and Yang D (2005) Alarmins: chemotactic activators of immune responses. Current Opinion in Immunology 17: 359–365.

Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. Journal of Leukocyte Biology 75: 39–48.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Wuerth, Kelli C, Hilchie, Ashley L, Brown, Kelly L, and Hancock, Robert EW(May 2013) Host Defence (Antimicrobial) Peptides and Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001212.pub3]