Mammalian defensins in the antimicrobial immune response

Nature Immunology

Volumn 6, Issue 6, 2005, Pages 551-557

  Selsted, Michael E ^a   Ouellette, Andre J ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA DEFENSIN; BACTERIAL DNA; BETA DEFENSIN; CATHELICIDIN; CYCLOPEPTIDE; CYTOKINE; DEFENSIN; DISULFIDE; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 1BETA; INTERLEUKIN 22; LIPOPEPTIDE; MATRILYSIN; MESSENGER RNA; MONOCLONAL ANTIBODY; OLIGOMER; OLIGONUCLEOTIDE; PHORBOL 13 ACETATE 12 MYRISTATE; PHOSPHOLIPID; PROTEIN HUMAN BETA DEFENSIN 1; PROTEIN HUMAN BETA DEFENSIN 2; PROTEIN HUMAN BETA DEFENSIN 3; PROTEIN HUMAN BETA DEFENSIN 4; PROTEIN KINASE C; THETA DEFENSIN; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ANTIBIOTIC RESISTANCE; ANTIMICROBIAL ACTIVITY; ATOPIC DERMATITIS; BACTERIAL MEMBRANE; BIOSYNTHESIS; BONE MARROW; CHROMOSOME 20; CRYSTAL STRUCTURE; EPITHELIUM; ESCHERICHIA COLI; FIBROBLAST; GENE DUPLICATION; GENE MUTATION; GENETIC VARIABILITY; GRANULOCYTE; HAEMOPHILUS INFLUENZAE; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; IMMUNOREACTIVITY; INNATE IMMUNITY; LEUKOCYTE; MAMMAL; MEMORY CELL; MUCOSA; MUTAGENESIS; NEUTROPHIL; NONHUMAN; ORTHOLOGY; PANETH CELL; PHAGOCYTE; PLANT; PRIORITY JOURNAL; PROTEIN EXPRESSION; PSORIASIS; RESPIRATORY TRACT INFLAMMATION; REVIEW; SALMONELLA TYPHIMURIUM; SKIN; SPERMATOZOON MATURATION; TARGET CELL; WILD TYPE; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; CLASSIFICATION; GENE EXPRESSION; GENETICS; IMMUNOLOGY;

ANIMALS; DEFENSINS; GENE EXPRESSION; HUMANS; IMMUNITY, NATURAL; MODELS, MOLECULAR; MOLECULAR STRUCTURE;

EID: 20644462344     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni1206     Document Type: Review

References (103)

1. Hoffmann, J.A., Kafatos, F.C., Janeway, C.A. & Ezekowitz, R.A. Phylogenetic perspectives in innate immunity. Science 284, 1313-1318 (1999).
2. Janeway, C.A., Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197-216 (2002).
3. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389-395 (2002).
4. Levy, O. Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J. Leukoc. Biol. 76, 909-925 (2004).
5. Yang, D., Biragyn, A., Hoover, D.M., Lubkowski, J. & Oppenheim, J.J. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu. Rev. Immunol. 22, 181-215 (2004).
6. Zanetti, M. Cathelicidins, multifunctional peptides of the innate immunity. J. Leukoc. Biol. 75, 39-48 (2004).
7. Ganz, T. Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 3, 710-720 (2003).
8. Lehrer, R.I. Primate defensins. Nat. Rev. Microbiol. 2, 727-738 (2004).
9. Schutte, B.C. & McCray, P.B., Jr. β-defensins in lung host defense. Annu. Rev. Physiol. 64, 709-748 (2002).
10. Patil, A., Hughes, A.L. & Zhang, G. Rapid evolution and diversification of mammalian alpha-defensins as revealed by comparative analysis of rodent and primate genes. Physiol. Genomics 20, 1-11 (2004).
11. Semple, C.A., Rolfe, M. & Dorin, J.R. Duplication and selection in the evolution of primate beta-defensin genes. Genome Biol. 4, R31 (2003).
12. Taudien, S. et al. Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence. BMC Genomics 5, 92 (2004).
13. Lynn, D.J., Lloyd, A.T., Fares, M.A. & O'Farrelly, C. Evidence of positively selected sites in mammalian α-defensins. Mol. Biol. Evol. 21, 819-827 (2004).
14. Leonova, L. et al. Circular minidefensins and posttranslational generation of molecular diversity. J. Leukoc. Biol. 70, 461-464 (2001).
15. Tang, Y.Q. et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated α-defensins. Science 286, 498-502 (1999).
16. Tran, D. et al. Homodimeric α-defensins from rhesus macaque leukocytes: isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J. Biol. Chem. 277, 3079-3084 (2002).
17. Nguyen, T.X., Cole, A.M. & Lehrer, R.I. Evolution of primate θ-defensins: a serpentine path to a sweet tooth. Peptides 24, 1647-1654 (2003).
18. Cole, A.M. et al. Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc. Natl. Acad. Sci. USA 99, 1813-1818 (2002).
19. Zeya, H.I. & Spitznagel, J.K. Antimicrobial specificity of leukocyte lysosomal cationic proteins. Science 154, 1049-1051 (1966).
20. Eisenhauer, P.B. & Lehrer, R.I. Mouse neutrophils lack defensins. Infect. Immun. 60, 3446-3447 (1992).
21. Mackewicz, C.E. et al. alpha-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS 17, F23-F32 (2003).
22. Chalifour, A. et al. Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers α-defensin production. Blood 104, 1778-1783 (2004).
23. Wilson, C.L. et al. Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286, 113-117 (1999).
24. Ghosh, D. et al. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat. Immunol. 3, 583-590 (2002).
25. Wu, E.R., Daniel, R. & Bateman, A. RK-2: a novel rabbit kidney defensin and its implications for renal host defense. Peptides 19, 793-799 (1998).
26. Satchell, D.P. et al. Interactions of mouse Paneth cell α-defensins and α-defensin precursors with membranes. Prosegment inhibition of peptide association with biomimetic membranes. J. Biol. Chem. 278, 13838-13846 (2003).
27. Valore, E.V. & Ganz, T. Posttranslational processing of defensins in immature human myeloid cells. Blood 79, 1538-1544 (1992).
28. Wu, Z. et al. From pro defensins to defensins: synthesis and characterization of human neutrophil pro α-defensin-1 and its mature domain. J. Pept. Res. 62, 53-62 (2003).
29. Daher, K.A., Selsted, M.E. & Lehrer, R.I. Direct inactivation of viruses by human granulocyte defensins. J. Virol. 60, 1068-1074 (1986).
30. Mandal, M. & Nagaraj, R. Antibacterial activities and conformations of synthetic α-defensin HNP-1 and analogs with one, two and three disulfide bridges. J. Pept. Res. 59, 95-104 (2002).
31. Maemoto, A. et al. Functional analysis of the α-defensin disulfide array in mouse cryptdin-4. J. Biol. Chem. 279, 44188-44196 (2004).
32. Wu, Z. et al. Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human β-defensin 3. Proc. Natl. Acad. Sci. USA 100, 8880-8885 (2003).
33. Diamond, G. et al. Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: Peptide isolation and cloning of a cDNA. Proc. Natl. Acad. Sci. USA 88, 3952-3956 (1991).
34. Diamond, G. & Bevins, C.L. Endotoxin upregulates expression of an antimicrobial peptide gene in mammalian airway epithelial cells. Chest 105, 51S-52S (1994).
35. Selsted, M.E. et al. Purification, primary structures, and antibacterial activities of β-defensins, a new family of antimicrobial peptides from bovine neutrophils. J. Biol. Chem. 268, 6641-6648 (1993).
36. Schutte, B.C. et al. Discovery of five conserved β-defensin gene clusters using a computational search strategy. Proc. Natl. Acad. Sci. USA 99, 2129-2133 (2002).
37. Rodriguez-Jimenez, F.J. et al. Distribution of new human β-defensin genes clustered on chromosome 20 in functionally different segments of epididymis. Genomics 81, 175-183 (2003).
38. Zhou, C.X. et al. An epididymis-specific β-defensin is important for the initiation of sperm maturation. Nat. Cell Biol. 6, 458-464 (2004).
39. Yudin, A.I. et al. ESP13.2, a member of the β-defensin family, is a macaque sperm surface-coating protein involved in the capacitation process. Biol. Reprod. 69, 1118-1128 (2003).
40. Bensch, K.W., Raida, M., Magert, H.J., Schulz-Knappe, P. & Forssmann, W.G. hBD-1: a novel β-defensin from human plasma. FEBS Lett. 368, 331-335 (1995).
41. Valore, E.V. et al. Human β-defensin-1: an antimicrobial peptide of urogenital tissues. J. Clin. Invest. 101, 1633-1642 (1998).
42. Harder, J., Bartels, J., Christophers, E. & Schroder, J.M. A peptide antibiotic from human skin. Nature 387, 861 (1997).
43. Harder, J., Bartels, J., Christophers, E. & Schroder, J.M. Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic. J. Biol. Chem. 276, 5707-5713 (2001).
44. Harder, J. & Schroder, J.M. Psoriatic scales: a promising source for the isolation of human skin-derived antimicrobial proteins. J. Leukoc. Biol. 77, 476-486 (2005).
45. Garcia, J.R. et al. Human β-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J. 15, 1819-1821 (2001).
46. Hiratsuka, T. et al. Increased concentrations of human β-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Thorax 58, 425-430 (2003).
47. Ross, D.J. et al. Increased bronchoalveolar lavage human β-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation. Transplantation 78, 1222-1224 (2004).
48. Ong, P.Y. et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N. Engl. J. Med. 347, 1151-1160 (2002).
49. Nomura, I. et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J. Immunol. 171, 3262-3269 (2003).
50. Ganz, T. Extracellular release of antimicrobial defensins by human polymorphonulear leukocytes. Infect. Immun. 55, 568-571 (1987).
51. 2+-activated, intermediate conductance potassium channel. J. Biol. Chem. 277, 3793-3800 (2002).
52. Rumio, C. et al. Degranulation of paneth cells via Toll-like receptor 9. Am. J. Pathol. 165, 373-381 (2004).
53. Duits, L.A., Ravensbergen, B., Rademaker, M., Hiemstra, P.S. & Nibbering, P.H. Expression of β-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106, 517-525 (2002).
54. Fang, X.M. et al. Differential expression of α- and β-defensins in human peripheral blood. Eur. J. Clin. Invest. 33, 82-87 (2003).
55. Harder, J., Meyer-Hoffert, U., Wehkamp, K., Schwichtenberg, L & Schroder, J.M. Differential gene induction of human β-defensins (hBD-1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid. J. Invest. Dermatol. 123, 522-529 (2004).
56. Singh, P.K. et al. Production of β-defensins by human airway epithelia. Proc. Natl. Acad. Sci. USA 95, 14961-14966 (1998).
57. Tsutsumi-Ishii, Y. & Nagaoka, I. Modulation of human β-defensin-2 transcription in pulmonary epithelial cells by lipopolysaccharide-stimulated mononuclear phagocytes via proinflammatorycytokine production. J. Immunol. 170, 4226-4236 (2003).
58. Liu, L., Roberts, A.A. & Ganz, T. By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide. J. Immunol. 170, 575-580 (2003).
59. 3 is a direct inducer of antimicrobial peptide gene expression. J. Immunol. 173, 2909-2912 (2004).
60. Wolk, K. et al. IL-22 increases the innate immunity of tissues. Immunity 21, 241-254 (2004).
61. Hertz, C.J. et al. Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human β defensin-2. J. Immunol. 171, 6820-6826 (2003).
62. Wang, X. et al. Airway epithelia regulate expression of human β-defensin 2 through Toll-like receptor 2. FASEB J. 17, 1727-1729 (2003).
63. Vora, P. et al. Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J. Immunol. 173, 5398-5405 (2004).
64. Schaefer, T.M., Fahey, J.V., Wright, J.A. & Wira, C.R. Innate immunity in the human female reproductive tract: antiviral response of uterine epithelial cells to the TLR3 agonist poly(I:C). J. Immunol. 174, 992-1002 (2005).
65. Proud, D., Sanders, S.P. & Wiehler, S. Human rhinovirus infection induces airway epithelial cell production of human β-defensin 2 both in vitro and in vivo. J. Immunol. 172, 4637-4645 (2004).
66. Platz, J. et al. Microbial DNA induces a host defense reaction of human respiratory epithelial cells. J. Immunol. 173, 1219-1223 (2004).
67. Chung, W.O., Hansen, S.R., Rao, D. & Dale, B.A. Protease-activated receptor signaling increases epithelial antimicrobial peptide expression. J. Immunol. 173, 5165-5170 (2004).
68. Ganz, T., Selsted, M.E. & Lehrer, R.I. Antimicrobial activity of phagocyte granule proteins. Sem. Resp. Infect. 1, 107-117 (1986).
69. Ayabe, T. et al. Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1, 113-118 (2000).
70. Salzman, N.H., Ghosh, D., Huttner, K.M., Paterson, Y. & Bevins, C.L. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422, 522-526 (2003).
71. Moser, C. et al. β-Defensin 1 contributes to pulmonary innate immunity in mice. Infect. Immun. 70, 3068-3072 (2002).
72. Morrison, G., Kilanowski, F., Davidson, D. & Dorin, J. Characterization of the mouse β defensin 1, Defb1, mutant mouse model. Infect. Immun. 70, 3053-3060 (2002).
73. Bader, M.W. et al. Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides. Mol. Microbiol. 50, 219-230 (2003).
74. Lehrer, R.I., Szklarek, D., Ganz, T. & Selsted, M.E. Correlation of binding of rabbit granulocyte peptides to Candida albicans with candidacidal activity. Infect. Immun. 49, 207-211 (1985).
75. Lehrer, R.I., Ganz, T., Szklarek, D. & Selsted, M.E. Modulation of the in vitro candidacidal activity of human neutrophil defensins by target cell metabolism and divalent cations. J. Clin. Invest. 81, 1829-1835 (1988).
76. Lehrer, R.I. et al. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J. Clin. Invest. 84, 553-561 (1989).
77. Boniotto, M. et al. A study of host defence peptide β-defensin 3 in primates. Biochem. J. 374, 707-714 (2003).
78. Edgerton, M. et al. Salivary histatin 5 and human neutrophil defensin 1 kill Candida albicans via shared pathways. Antimicrob. Agents Chemother. 44, 3310-3316 (2000).
79. Helmerhorst, E.J. et al. The cellular target of histatin 5 on Candida albicans is the energized mitochondrion. J. Biol. Chem. 274, 7286-7291 (1999).
80. Sahl, H.G. et al. Mammalian defensins: structures and mechanism of antibiotic activity. J. Leukoc. Biol. 77, 466-475 (2005).
81. Panyutich, A.V., Voitenok, N.N., Lehrer, R.I. & Ganz, T. An enzyme immunoassay for human defensins. J. Immunol. Methods 141, 149-155 (1991).
82. Kagan, B.L., Selsted, M.E., Ganz, T. & Lehrer, R.I. antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc. Natl. Acad. Sci. USA 87, 210-214 (1990).
83. Lohner, K., Latal, A., Lehrer, R.I. & Ganz, T. Differential scanning microcalorimetry indicates that human defensin, HNP-2, interacts specifically with biomembrane mimetic systems. Biochemistry 36, 1525-1531 (1997).
84. Wimley, W.C., Selsted, M.E. & White, S.H. Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores. Protein Sci. 3, 1362-1373 (1994).
85. Hristova, K., Selsted, M.E. & White, S.H. Critical role of lipid composition in membrane permeabilization by rabbit neutrophil defensins. J. Biol. Chem. 272, 24224-24233 (1997).
86. Trabi, M., Schirra, H.J. & Craik, D.J. Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes. Biochemistry 40, 4211-4221 (2001).
87. Abuja, P.M., Zenz, A., Trabi, M., Craik, D.J. & Lohner, K. The cyclic antimicrobial peptide RTD-1 induces stabilized lipid-peptide domains more efficiently than its open-chain analogue. FEBS Lett. 566, 301-306 (2004).
88. Weiss, T.M. et al. Two states of cyclic antimicrobial peptide RTD-1 in lipid bilayers. Biochemistry 41, 10070-10076 (2002).
89. Buffy, J.J. et al. Solid-state NMR investigation of the selective perturbation of lipid bilayers by the cyclic antimicrobial peptide RTD-1. Biochemistry 43, 9800-9812 (2004).
90. Munk, C. et al. The θ-defensin, retrocyclin, inhibits HIV-1 entry. AIDS Res. Hum. Retroviruses 19, 875-881 (2003).
91. Wang, W., Cole, A.M., Hong, T., Waring, A.J. & Lehrer, R.I. Retrocyclin, an antiretroviral θ-defensin, is a lectin. J. Immunol. 170, 4708-4716 (2003).
92. Territo, M.C., Ganz, T., Selsted, M.E. & Lehrer, R.I. Monocyte-chemotactic activity of defensins from human neutrophils. J. Clin. Invest. 84, 2017-2020 (1989).
93. Chertov, O. et al. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J. Biol. Chem. 271, 2935-2940 (1996).
94. Yang, D., Chen, Q., Chertov, O. & Oppenheim, J.J. Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J. Leukoc. Biol. 68, 9-14 (2000).
95. Yang, D. et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286, 525-528 (1999).
96. Garcia, J.R. et al. Identification of a novel, multifunctional β-defensin (human β-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res. 306, 257-264 (2001).
97. Yang, D., Biragyn, A., Kwak, L.W. & Oppenheim, J.J. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 23, 291-296 (2002).
98. Befus, A.D. et al. Neutrophil defensins induce histamine secretion from mast cells: mechanisms of action. J. Immunol. 163, 947-953 (1999).
99. Niyonsaba, F., Iwabuchi, K., Matsuda, H., Ogawa, H. & Nagaoka, I. Epithelial cell-derived human β-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int. Immunol. 14, 421-426 (2002).
100. Murphy, C.J., Foster, B.A., Mannis, M.J., Selsted, M.E. & Reid, T.W. Defensins are mitogenic for epithelial cells and fibroblasts. J. Cell. Physiol. 155, 408-413 (1993).
101. Aarbiou, J. et al. Human neutrophil defensins induce lung epithelial cell proliferation in vitro. J. Leukoc. Biol. 72, 167-174 (2002).
102. Chavakis, T. et al. Regulation of neovascularization by human neutrophil peptides (α-defensins): a link between inflammation and angiogenesis. FASEB J. 18, 1306-1308 (2004).
103. Aarbiou, J. et al. Neutrophil defensins enhance lung epithelial wound closure and mucin gene expression in vitro. Am. J. Respir. Cell Mol. Biol. 30, 193-201 (2004).