Multifaceted Immune Functions of Human Defensins and Underlying Mechanisms

Overview

Journal Semin Cell Dev Biol

Specialties Cell Biology
Reproductive Medicine

Date 2018 Mar 5

PMID 29501617

Citations 63

Authors

Saahil Fruitwala

Darine W El-Naccache

Theresa L Chang

Affiliations

Soon will be listed here.

Abstract

Defensins have been long recognized as natural antimicrobial peptides, but they also possess diverse and versatile immune functions. Defensins can both induce inflammation and suppress inflammatory responses by acting on specific cells through distinct mechanisms. Defensins can also modulate the immune response by forming a complex with cellular molecules including proteins, nucleic acids, and carbohydrates. The mechanisms of defensin-mediated immune modulation appear to be cell-type and context specific. Because the levels of human defensins are often altered in response to infection or disease states, suggesting their clinical relevance, this review summarizes the complex immune functions of human defensins and their underlying mechanisms of action, which have implications for the development of new therapeutics.

Citing Articles

HAS-CIRCpedia-5280 sponges miR-4712-5p inhibited colon cancer autophagyinduced by human beta-defensin-1.

An S, Cui J, Yang W, Zhang M, Yu H, Lu J J Transl Med. 2025; 23(1):281.

PMID: 40050987 PMC: 11883960. DOI: 10.1186/s12967-024-05860-x.

Alpha-defensins increase NTHi binding but not engulfment by the macrophages enhancing airway inflammation in Alpha-1 antitrypsin deficiency.

Lee J, Mohammad N, Han K, Flagg-Dowie T, Magallon M, Brantly M Front Immunol. 2025; 16:1543729.

PMID: 40013145 PMC: 11861504. DOI: 10.3389/fimmu.2025.1543729.

Human Defensins: Structure, Function, and Potential as Therapeutic Antimicrobial Agents with Highlights Against SARS CoV-2.

Nagib M, Sayed A, Korany A, Abdelkader K, Shari F, Mackay W Probiotics Antimicrob Proteins. 2024; .

PMID: 39693007 DOI: 10.1007/s12602-024-10436-8.

Discovery of bioactive peptides as therapeutic agents for skin wound repair.

Fadilah N, Shahabudin N, Mohd Razif R, Sanyal A, Ghosh A, Baharin K J Tissue Eng. 2024; 15:20417314241280359.

PMID: 39398382 PMC: 11468004. DOI: 10.1177/20417314241280359.

DEFB119 stratifies dysbiosis with distorted networks in the seminal microbiome associated with male infertility.

Jin J, Yim H, Chang H, Wang Y, Choy K, Chan S PNAS Nexus. 2024; 3(10):pgae419.

PMID: 39359400 PMC: 11443970. DOI: 10.1093/pnasnexus/pgae419.

References

Kao C, Kim C, Huang F, Wu R . Requirements for two proximal NF-kappaB binding sites and IkappaB-zeta in IL-17A-induced human beta-defensin 2 expression by conducting airway epithelium. J Biol Chem. 2008; 283(22):15309-18. PMC: 2397472. DOI: 10.1074/jbc.M708289200. View

Kanda N, Watanabe S . Increased serum human β-defensin-2 levels in atopic dermatitis: relationship to IL-22 and oncostatin M. Immunobiology. 2011; 217(4):436-45. DOI: 10.1016/j.imbio.2011.10.010. View

Ganz T . Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003; 3(9):710-20. DOI: 10.1038/nri1180. View

Albanesi C, Fairchild H, Madonna S, Scarponi C, De Pita O, Leung D . IL-4 and IL-13 negatively regulate TNF-alpha- and IFN-gamma-induced beta-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3. J Immunol. 2007; 179(2):984-92. DOI: 10.4049/jimmunol.179.2.984. View

Yang D, Chen Q, Chertov O, Oppenheim J . Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J Leukoc Biol. 2000; 68(1):9-14. View

Biswas A, Liu Y, Hao L, Mizoguchi A, Salzman N, Bevins C . Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum. Proc Natl Acad Sci U S A. 2010; 107(33):14739-44. PMC: 2930434. DOI: 10.1073/pnas.1003363107. View

Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang Y, Homey B . Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007; 449(7162):564-9. DOI: 10.1038/nature06116. View

Meisch J, Vogel R, Schlatzer D, Li X, Chance M, Levine A . Human β-defensin 3 induces STAT1 phosphorylation, tyrosine phosphatase activity, and cytokine synthesis in T cells. J Leukoc Biol. 2013; 94(3):459-71. PMC: 3747125. DOI: 10.1189/jlb.0612300. View

Otte J, Werner I, Brand S, Chromik A, Schmitz F, Kleine M . Human beta defensin 2 promotes intestinal wound healing in vitro. J Cell Biochem. 2008; 104(6):2286-97. DOI: 10.1002/jcb.21787. View

10.

Weinberg A, Jin G, Sieg S, McCormick T . The yin and yang of human Beta-defensins in health and disease. Front Immunol. 2012; 3:294. PMC: 3465815. DOI: 10.3389/fimmu.2012.00294. View

11.

Yang D, Biragyn A, Hoover D, Lubkowski J, Oppenheim J . Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 2004; 22:181-215. DOI: 10.1146/annurev.immunol.22.012703.104603. View

12.

Chertov O, Michiel D, Xu L, Wang J, Tani K, Murphy W . Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem. 1996; 271(6):2935-40. DOI: 10.1074/jbc.271.6.2935. View

13.

Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L . Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol. 2005; 124(5):931-8. DOI: 10.1111/j.0022-202X.2005.23705.x. View

14.

Ganz T . Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytes. Infect Immun. 1987; 55(3):568-71. PMC: 260375. DOI: 10.1128/iai.55.3.568-571.1987. View

15.

Miles K, Clarke D, Lu W, Sibinska Z, Beaumont P, Davidson D . Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol. 2009; 183(3):2122-32. PMC: 2948539. DOI: 10.4049/jimmunol.0804187. View

16.

Feng Z, Dubyak G, Lederman M, Weinberg A . Cutting edge: human beta defensin 3--a novel antagonist of the HIV-1 coreceptor CXCR4. J Immunol. 2006; 177(2):782-6. DOI: 10.4049/jimmunol.177.2.782. View

17.

Jin G, Kawsar H, Hirsch S, Zeng C, Jia X, Feng Z . An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2, a model for tumorigenesis. PLoS One. 2010; 5(6):e10993. PMC: 2882331. DOI: 10.1371/journal.pone.0010993. View

18.

Mackewicz C, Yuan J, Tran P, Diaz L, Mack E, Selsted M . alpha-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS. 2003; 17(14):F23-32. DOI: 10.1097/00002030-200309260-00001. View

19.

Lioi A, Rodriguez A, Funderburg N, Feng Z, Weinberg A, Sieg S . Membrane damage and repair in primary monocytes exposed to human β-defensin-3. J Leukoc Biol. 2012; 92(5):1083-91. PMC: 4050522. DOI: 10.1189/jlb.0112046. View

20.

Huang F, Kao C, Wachi S, Thai P, Ryu J, Wu R . Requirement for both JAK-mediated PI3K signaling and ACT1/TRAF6/TAK1-dependent NF-kappaB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells. J Immunol. 2007; 179(10):6504-13. DOI: 10.4049/jimmunol.179.10.6504. View