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Defensins in innate immunity

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Abstract

The innate immune system is the first line of defense against many common microorganisms, which can initiate adaptive immune responses to provide increased protection against subsequent re-infection by the same pathogen. As a major family of antimicrobial peptides, defensins are widely expressed in a variety of epithelial cells and sometimes in leukocytes, playing an important role in the innate immune system due to their antimicrobial, chemotactic and regulatory activities. This review introduces their structure, classification, distribution, synthesis, and focuses on their biological activities and mechanisms, as well as clinical relevance. These studies of defensins in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including bacterial ocular disease.

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References

  • Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jörnvall H, Wigzell H, Gudmundsson GH (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96(9):3086–3093

    CAS  PubMed  Google Scholar 

  • Ashitani J, Mukae H, Hiratsuka T, Nakazato M, Kumamoto K, Matsukura S (2002) Elevated levels of alpha-defensins in plasma and BAL fluid of patients with active pulmonary tuberculosis. Chest 121(2):519–526

    CAS  PubMed  Google Scholar 

  • Bai Y, Liu S, Jiang P, Zhou L, Li J, Tang C, Verma C, Mu Y, Beuerman RW, Pervushin K (2009) Structure–dependent charge density as a determinant of antimicrobial activity of peptide analogues of defensin. Biochemistry 48(30):7229–7239

    CAS  PubMed  Google Scholar 

  • Bals R (2000) Epithelial antimicrobial peptides in host defense against infection. Respir Res 1:141–150

    CAS  PubMed  Google Scholar 

  • Bals R, Wang X, Meegalla RL, Wattler S, Weiner DJ, Nehls MC, Wilson JM (1999) Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs. Infect Immun 67(7):3542–3547

    CAS  PubMed  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252

    CAS  PubMed  Google Scholar 

  • Baroni A, Donnarumma G, Paoletti I, Longanesi-Cattani I, Bifulco K, Tufano MA, Carriero MV (2009) Antimicrobial human beta-defensin-2 stimulates migration, proliferation and tube formation of human umbilical vein endothelial cells. Peptides 30(2):267–272

    CAS  PubMed  Google Scholar 

  • Bharathi MJ, Ramakrishnan R, Meenakshi R, Kumar CS, Padmavathy S, Mittal S (2007) Ulcerative keratitis associated with contact lens wear. Indian J Ophthalmol 55(1):64–67

    PubMed  Google Scholar 

  • Biragyn A, Surenhu M, Yang D, Ruffini PA, Haines BA, Klyushnenkova E, Oppenheim JJ, Kwak LW (2001) Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens. J Immunol 167:6644–6653

    CAS  PubMed  Google Scholar 

  • Biragyn A, Belyakov IM, Chow YH, Dimitrov DS, Berzofsky JA, Kwak LW (2002a) DNA vaccines encoding HIV-1 gp120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses. Blood 100:1153–1159

    CAS  PubMed  Google Scholar 

  • Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW (2002b) Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298(5595):1025–1029

    CAS  PubMed  Google Scholar 

  • Biragyn A, Coscia M, Nagashima K, Sanford M, Young HA, Olkhanud P (2008) Murine beta-defensin 2 promotes TLR-4/MyD88-mediated and NF-kappaB-dependent atypical death of APCs via activation of TNFR2. J Leukoc Biol 83(4):998–1008

    CAS  PubMed  Google Scholar 

  • Boman HG (2003) Antimicrobial peptides: basic facts and emerging concepts. J Intern Med 254:197–215

    CAS  PubMed  Google Scholar 

  • Chalifour A, Jeannin P, Gauchat JF, Blaecke A, Malissard M, N'Guyen T, Thieblemont N, Delneste Y (2004) Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood 104(6):1778–1783

    CAS  PubMed  Google Scholar 

  • Chang TL, Vargas J, DelPortillo A, Klotman ME (2005) Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 115(3):765–773

    CAS  PubMed  Google Scholar 

  • Chen XM, O'Hara SP, Nelson JB, Splinter PL, Small AJ, Tietz PS, Limper AH, LaRusso NF (2005) Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-kappaB. J Immunol 175(11):7447–7456

    CAS  PubMed  Google Scholar 

  • Chong KT, Thangavel RR, Tang X (2008) Enhanced expression of murine beta-defensins (MBD-1, -2,- 3, and -4) in upper and lower airway mucosa of influenza virus infected mice. Virology 380(1):136–143

    CAS  PubMed  Google Scholar 

  • Cole AM, Hong T, Boo LM, Nguyen T, Zhao C, Bristol G, Zack JA, Waring AJ, Yang OO, Lehrer RI (2002) Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci USA 99(4):1813–1818

    CAS  PubMed  Google Scholar 

  • Daher KA, Selsted ME, Lehrer RI (1986) Direct inactivation of viruses by human granulocyte defensins. J Virol 60(3):1068–1074

    CAS  PubMed  Google Scholar 

  • da Silva Correia CJ, Soldau K, Christen U, Tobias PS, Ulevitch RJ (2001) Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. Transfer from CD14 to TLR4 and MD-2. J Biol Chem 276:21129–21135

    PubMed  Google Scholar 

  • de Leeuw E, Li C, Zeng P, Li C, Diepeveen-de Buin M, Lu WY, Breukink E, Lu W (2010) Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II. FEBS Lett 584(8):1543–1548

    PubMed  Google Scholar 

  • Droin N, Hendra JB, Ducoroy P, Solary E (2009) Human defensins as cancer biomarkers and antitumour molecules. J Proteomics 72(6):918–927

    CAS  PubMed  Google Scholar 

  • Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH (2002) Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106(4):517–525

    CAS  PubMed  Google Scholar 

  • Ericksen B, Wu Z, Lu W, Lehrer RI (2005) Antibacterial activity and specificity of the six human alpha-defensins. Antimicrob Agents Chemother 49(1):269–275

    CAS  PubMed  Google Scholar 

  • Feng Z, Jiang B, Chandra J, Ghannoum M, Nelson S, Weinberg A (2005) Human beta-defensins: differential activity against Candidal species and regulation by Candida albicans. J Dent Res 84:445–450

    CAS  PubMed  Google Scholar 

  • Funderburg N, Lederman MM, Feng Z, Drage MG, Jadlowsky J, Harding CV, Weinberg A, Sieg SF (2007) Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc Natl Acad Sci USA 104(47):18631–18635

    CAS  PubMed  Google Scholar 

  • Ganz T (2003) Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3(9):710–720

    CAS  PubMed  Google Scholar 

  • García JR, Jaumann F, Schulz S, Krause A, Rodríguez-Jiménez J, Forssmann U, Adermann K, Klüver E, Vogelmeier C, Becker D, Hedrich R, Forssmann WG, Bals R (2001a) Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res 306(2):257–264

    PubMed  Google Scholar 

  • García JR, Krause A, Schulz S, Rodríguez-Jiménez FJ, Klüver E, Adermann K, Forssmann U, Frimpong-Boateng A, Bals R, Forssmann WG (2001b) Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 15(10):1819–1821

    PubMed  Google Scholar 

  • Greenwald GI, Ganz T (1987) Defensins mediate the microbicidal activity of human neutrophil granule extract against Acinetobacter calcoaceticus. Infect Immun 55(6):1365–1368

    CAS  PubMed  Google Scholar 

  • Hancock RE (1997) Peptide antibiotics. Lancet 349(9049):418–422

    CAS  PubMed  Google Scholar 

  • Harder J, Meyer-Hoffert U, Teran LM, Schwichtenberg L, Bartels J, Maune S, Schröder JM (2000) Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. Am J Respir Cell Mol Biol 22(6):714–721

    CAS  PubMed  Google Scholar 

  • Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276(8):5707–5713

    CAS  PubMed  Google Scholar 

  • Haynes RJ, Tighe PJ, Dua HS (1999) Antimicrobial defensin peptides of the human ocular surface. Br J Ophthalmol 83(6):737–741

    CAS  PubMed  Google Scholar 

  • Hazlett LD (2004) Corneal response to Pseudomonas aeruginosa infection. Prog Retin Eye Res 23:1–30

    CAS  PubMed  Google Scholar 

  • Hazlett LD, McClellan S, Kwon B, Barrett R (2000) Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Th1 versus Th2 responsive. Invest Ophthalmol Vis Sci 41:805–810

    CAS  PubMed  Google Scholar 

  • Hazlett LD, McClellan SA, Barrett RP, Liu J, Zhang Y, Lighvani S (2007) Spantide I decreases type I cytokines, enhances IL-10, and reduces corneal perforation in susceptible mice after Pseudomonas aeruginosa infection. Invest Ophthalmol Vis Sci 48:797–807

    PubMed  Google Scholar 

  • Hazrati E, Galen B, Lu W, Wang W, Ouyang Y, Keller MJ, Lehrer RI, Herold BC (2006) Human alpha- and beta-defensins block multiple steps in herpes simplex virus infection. J Immunol 177(12):8658–8666

    CAS  PubMed  Google Scholar 

  • Hornef MW, Frisan T, Vandewalle A, Normark S, Richter-Dahlfors A (2002) Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med 195:559–570

    CAS  PubMed  Google Scholar 

  • Hoover DM, Rajashankar KR, Blumenthal R, Puri A, Oppenheim JJ, Chertov O, Lubkowski J (2000) The structure of human beta-defensin-2 shows evidence of higher order oligomerization. J Biol Chem 275(42):32911–32918

    CAS  PubMed  Google Scholar 

  • Janeway CA, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216

    CAS  PubMed  Google Scholar 

  • Jia HP, Schuttea BC, Schudye A, Linzmeierf R, Guthmillerd JM, Johnsond GK, Tackc BF, Mitrosa JP, Rosenthale A,Ganzf T, McCray PB Jr (2001) Discovery of new human b-defensins using a genomics-based approach. Gene 263: 211–218

    Google Scholar 

  • Joly S, Organ CC, Johnson GK, McCray PB, Guthmiller JM (2005) Correlation between beta-defensin expression and induction profiles in gingival keratinocytes. Mol Immunol 42(9):1073–1084

    CAS  PubMed  Google Scholar 

  • Kesting MR, Loeffelbein DJ, Hasler RJ, Wolff KD, Rittig A, Schulte M, Hirsch T, Wagenpfeil S, Jacobsen F, Steinstraesser L (2009) Expression profile of human beta-defensin 3 in oral squamous cell carcinoma. Cancer Invest 27(5):575–581

    CAS  PubMed  Google Scholar 

  • Kisich KO, Heifets L, Higgins M, Diamond G (2001) Antimycobacterial agent based on mRNA encoding human beta-defensin 2 enables primary macrophages to restrict growth of Mycobacterium tuberculosis. Infect Immun 69(4):2692–2699

    CAS  PubMed  Google Scholar 

  • Kreuter A, Skrygan M, Gambichler T, Brockmeyer NH, Stücker M, Herzler C, Potthoff A, Altmeyer P, Pfister H, Wieland U (2009) Human papillomavirus-associated induction of human beta-defensins in anal intraepithelial neoplasia. Br J Dermatol 160(6):1197–1205

    CAS  PubMed  Google Scholar 

  • Krishnakumari V, Nagaraj R (2008) Interaction of antibacterial peptides spanning the carboxy-terminal region of human beta-defensins 1-3 with phospholipids at the air-water interface and inner membrane of E. coli. Peptides 29(1):7–14

    CAS  PubMed  Google Scholar 

  • Kumar A, Yin J, Zhang J, Yu FS (2007) Modulation of corneal epithelial innate immune response to pseudomonas infection by flagellin pretreatment. Invest Ophthalmol Vis Sci 48(10):4664–4670

    PubMed  Google Scholar 

  • Lai Y, Gallo RL (2009) AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 30(3):131–141

    CAS  PubMed  Google Scholar 

  • Leitch GJ, Ceballos C (2009) A role for antimicrobial peptides in intestinal microsporidiosis. Parasitology 136(2):175–181

    CAS  PubMed  Google Scholar 

  • Lehrer RI (2004) Primate defensins. Nat Rev Microbiol 2(9):727–738

    CAS  PubMed  Google Scholar 

  • Liu L, Roberts AA, Ganz T (2003) By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide. J Immunol 170(1):575–580

    CAS  PubMed  Google Scholar 

  • Lu Q, Darveau RP, Samaranayake LP, Wang CY, Jin L (2009) Differential modulation of human {beta}-defensins expression in human gingival epithelia by Porphyromonas gingivalis lipopolysaccharide with tetra- and penta-acylated lipid A structures. Innate Immun 15(6):325–335

    CAS  PubMed  Google Scholar 

  • Madison MN, Kleshchenko YY, Nde PN, Simmons KJ, Lima MF, Villalta F (2007) Human defensin alpha-1 causes Trypanosoma cruzi membrane pore formation and induces DNA fragmentation, which leads to trypanosome destruction. Infect Immun 75(10):4780–4791

    CAS  PubMed  Google Scholar 

  • Mallow EB, Harris A, Salzman N, Russell JP, DeBerardinis RJ, Ruchelli E, Bevins CL (1996) Human enteric defensins. Gene structure and developmental expression. J Biol Chem 271(8):4038–4045

    CAS  PubMed  Google Scholar 

  • Matsuzaki K (1999) Why and how are peptide-lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes. Biochem Biophys Acta 1462:1–10

    CAS  PubMed  Google Scholar 

  • McDermott AM (2004) Defensins and other antimicrobial peptides at the ocular surface. Ocul Surf 2:229–247

    PubMed  Google Scholar 

  • McDermott AM (2009) The role of antimicrobial peptides at the ocular surface. Ophthalmic Res 41(2):60–75

    CAS  PubMed  Google Scholar 

  • McDermott AM, Redfern RL, Zgang B, Pei Y, Huang L, Proske RJ (2003) Defensin expression by the cornea: Multiple signaling pathways mediate IL-1b stimulation of hBD-2 expression by human corneal epithelial cells. Invest Ophthalmol Vis Sci 44:1859–1865

    PubMed  Google Scholar 

  • Medzhitov R, Janeway CA (1997) Innate immunity: the virtues of a nonclonal system of recognition. Cell 91(3):295–298

    CAS  PubMed  Google Scholar 

  • Medzhitov R, Janeway CA (2000a) Innate Immunity. N Engl J Med 343(5):339–344

    Google Scholar 

  • Medzhitov R, Janeway CA (2000b) How does the immune system distinguish self from nonself? Semin Immunol 12(3):185–188

    CAS  PubMed  Google Scholar 

  • Miles K, Clarke DJ, Lu W, Sibinska Z, Beaumont PE, Davidson DJ, Barr TA, Campopiano DJ, Gray M (2009) Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol 183(3):2122–2132

    CAS  PubMed  Google Scholar 

  • Mothes H, Melle C, Ernst G, Kaufmann R, von Eggeling F, Settmacher U (2008) Human Neutrophil Peptides 1–3–early markers in development of colorectal adenomas and carcinomas. Dis Markers 25(2):123–129

    CAS  PubMed  Google Scholar 

  • Munk C, Wei G, Yang OO, Waring AJ, Wang W, Hong T, Lehrer RI, Landau NR, Cole AM (2003) The theta-defensin, retrocyclin, inhibits HIV-1 entry. AIDS Res Hum Retroviruses 19(10):875–881

    PubMed  Google Scholar 

  • Nagaoka I, Niyonsaba F, Tsutsumi-Ishii Y, Tamura H, Hirata M (2008) Evaluation of the effect of human beta-defensins on neutrophil apoptosis. Int Immunol 20(4):543–553

    CAS  PubMed  Google Scholar 

  • Negroni A, Stronati L, Pierdomenico M, Tirindelli D, Di Nardo G, Mancini V, Maiella G, Cucchiara S (2009) Activation of NOD2-mediated intestinal pathway in a pediatric population with Crohn's disease. Inflamm Bowel Dis 15(8):1145–1154

    PubMed  Google Scholar 

  • Nguyen TX, Cole AM, Lehrer RI (2003) Evolution of primate theta-defensins: a serpentine path to a sweet tooth. Peptides 24(11):1647–1654

    CAS  PubMed  Google Scholar 

  • Niyonsaba F, Iwabuchi K, Matsuda H, Ogawa H, Nagaoka I (2002) 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

    CAS  PubMed  Google Scholar 

  • Niyonsaba F, Ogawa H, Nagaoka I (2004) Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology 111(3):273–281

    CAS  PubMed  Google Scholar 

  • Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, Nagaoka I, Okumura K, Ogawa H (2007) Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 127(3):594–604

    CAS  PubMed  Google Scholar 

  • Oppenheim JJ, Yang D (2005) Alarmins: chemotactic activators of immune responses. Curr Opin Immunol 17(4):359–365

    CAS  PubMed  Google Scholar 

  • Ouhara K, Komatsuzawa H, Yamada S, Shiba H, Fujiwara T, Ohara M, Sayama K, Hashimoto K, Kurihara H, Sugai M (2005) Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, {beta}-defensins and LL37, produced by human epithelial cells. J Antimicrob Chemother 55(6):888–896

    CAS  PubMed  Google Scholar 

  • Palucka K, Banchereau J (2002) How dendritic cells and microbes interact to elicit or subvert protective immune responses. Curr Opin Immunol 14(4):420–431

    CAS  PubMed  Google Scholar 

  • Papanastasiou EA, Hua Q, Sandouk A, Son UH, Christenson AJ, Van Hoek ML, Bishop BM (2009) Role of acetylation and charge in antimicrobial peptides based on human beta-defensin-3. APMIS 117(7):492–499

    CAS  PubMed  Google Scholar 

  • Rivas-Santiago B, Schwander SK, Sarabia C, Diamond G, Klein-Patel ME, Hernandez-Pando R, Ellner JJ, Sada E (2005) Human {beta}-defensin 2 is expressed and associated with Mycobacterium tuberculosis during infection of human alveolar epithelial cells. Infect Immun 73(8):4505–4511

    CAS  PubMed  Google Scholar 

  • Rivas-Santiago B, Sada E, Tsutsumi V, Aguilar-Leon D, Contreras JL, Hernandez-Pando R (2006) beta-Defensin gene expression during the course of experimental tuberculosis infection. J Infect Dis 194(5):697–701

    CAS  PubMed  Google Scholar 

  • Rodríguez-García M, Oliva H, Climent N, García F, Gatell JM, Gallart T (2007) Human immature monocyte-derived dendritic cells produce and secrete alpha-defensins 1-3. J Leukoc Biol 82(5):1143–1146

    PubMed  Google Scholar 

  • Rohrl J, Yand D, Oppenheim JJ, Hehlgans T (2010) Human β-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J Immunol 184:6688–6694

    CAS  PubMed  Google Scholar 

  • Ryan L, Diamond G (2010) Mouse beta-defensin-1 plays a role in influenza innate immunity. J Immunol 184:37–49

    Google Scholar 

  • Schein OD, Ormerod LD, Barraquer E, Alfonso E, Egan KM, Paton BG, Kenyon KR (1989) Microbiology of contact lens-related keratitis. Cornea 8(4):281–285

    CAS  PubMed  Google Scholar 

  • Schröder JM, Harder J (1999) Human beta-defensin-2. Int J Biochem Cell Biol 31(6):645–651

    PubMed  Google Scholar 

  • Schutte BC, McCray PB (2002) Beta-defensins in lung host defense. Annu Rev Physiol 64:709–748

    CAS  PubMed  Google Scholar 

  • Scudiero O, Galdiero S, Cantisani M, Di Noto R, Vitiello M, Galdiero M, Naclerio G, Cassiman JJ, Pedone C, Castaldo G, Salvatore F (2010) Novel synthetic, salt-resistant analogs of human beta-defensins 1 and 3 endowed with enhanced antimicrobial activity. Antimicrob Agents Chemother. Epub Mar 22

  • Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6(6):551–557

    CAS  PubMed  Google Scholar 

  • Sharma S, Verma I, Khuller GK (2000) Antibacterial activity of human neutrophil peptide-1 against Mycobacterium tuberculosis H37Rv: in vitro and ex vivo study. Eur Respir J 16(1):112–117

    CAS  PubMed  Google Scholar 

  • Sharma S, Verma I, Khuller GK (2001) Therapeutic potential of human neutrophil peptide 1 against experimental tuberculosis. Antimicrob Agents Chemother 45(2):639–640

    CAS  PubMed  Google Scholar 

  • Soehnlein O, Kai-Larsen Y, Frithiof R, Sorensen OE, Kenne E, Scharffetter-Kochanek K, Eriksson EE, Herwald H, Agerberth B, Lindbom L (2008) Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest 118(10):3491–3502

    CAS  PubMed  Google Scholar 

  • Sumikawa Y, Asada H, Hoshino K, Azukizawa H, Katayama I, Akira S, Itami S (2006) Induction of beta-defensin 3 in keratinocytes stimulated by bacterial lipopeptides through toll-like receptor 2. Microbes Infect 8(6):1513–1521

    CAS  PubMed  Google Scholar 

  • Suresh A, Verma C (2006) Modelling study of dimerization in mammalian defensins. BMC Bioinform 7(Suppl 5):S17

    Google Scholar 

  • Syeda F, Tullis E, Slutsky AS, Zhang H (2008) Human neutrophil peptides upregulate expression of COX-2 and endothelin-1 by inducing oxidative stress. Am J Physiol Heart Circ Physiol 294(6):H2769–H2774

    CAS  PubMed  Google Scholar 

  • Tanaka T, Rahman MM, Battur B, Boldbaatar D, Liao M, Umemiya-Shirafuji R, Xuan X, Fujisaki K (2010) Parasiticidal activity of human alpha-defensin-5 against Toxoplasma gondii. In Vitro Cell Dev Biol Anim Epub Feb 5.

  • Territo MC, Ganz T, Selsted ME, Lehrer R (1989) Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 84(6):2017–2020

    CAS  PubMed  Google Scholar 

  • Tomita T, Nagase T (2001) Defensins as a mechanism of host defense and innate immunity. Nippon Ronen Igakkai Zasshi 38(4):440–443

    CAS  PubMed  Google Scholar 

  • Tongaonkar P, Selsted ME (2009) SDF2L1, a component of the endoplasmic reticulum chaperone complex, differentially interacts with {alpha}-, {beta}-, and {theta}-defensin propeptides. J Biol Chem 284(9):5602–5609

    CAS  PubMed  Google Scholar 

  • Tsutsumi-Ishii Y, Nagaoka I (2002) NF-κB-mediated transcriptional regulation of human β-defensin-2 gene following lipopolysaccharide stimulation. J Leukoc Biol 71:154–162

    CAS  PubMed  Google Scholar 

  • Uehara A, Fujimoto Y, Fukase K, Takada H (2007) Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol 44(12):3100–3111

    CAS  PubMed  Google Scholar 

  • Valore EV, Martin E, Harwig SS, Ganz T (1996) Intramolecular inhibition of human defensin HNP-1 by its propiece. J Clin Invest 97(7):1624–1629

    CAS  PubMed  Google Scholar 

  • Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T (1998) Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101(8):1633–1642

    CAS  PubMed  Google Scholar 

  • van 't Hof W, Veerman EC, Helmerhorst EJ, Amerongen AV (2001) Antimicrobial peptides: properties and applicability. Biol Chem 382(4):597–619

    PubMed  Google Scholar 

  • Varoga D, Wruck CJ, Tohidnezhad M, Brandenburg L, Paulsen F, Mentlein R, Seekamp A, Besch L, Pufe T (2009) Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3. Histochem Cell Biol 131(2):207–218

    CAS  PubMed  Google Scholar 

  • Verma C, Seebah S, Low SM, Zhou L, Liu SP, Li J, Beuerman RW (2007) Defensins: antimicrobial peptides for therapeutic development. Biotechnol J 2(11):1353–1359

    CAS  PubMed  Google Scholar 

  • Vora P, Youdim A, Thomas LS, Fukata M, Tesfay SY, Lukasek K, Michelsen KS, Wada A, Hirayama T, Arditi M, Abreu MT (2004) Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J Immunol 173(9):5398–5405

    CAS  PubMed  Google Scholar 

  • Vylkova S, Nayyar N, Li W, Edgerton M (2007) Human beta-defensins kill Candida albicans in an energy-dependent and salt-sensitive manner without causing membrane disruption. Antimicrob Agents Chemother 51(1):154–161

    CAS  PubMed  Google Scholar 

  • Wang W, Cole AM, Hong T, Waring AJ, Lehrer RI (2003) Retrocyclin, an antiretroviral theta-defensin, is a lectin. J Immunol 170(9):4708–4716

    CAS  PubMed  Google Scholar 

  • Wang W, Owen SM, Rudolph DL, Cole AM, Hong T, Waring AJ, Lal RB, Lehrer RI (2004) Activity of alpha- and theta-defensins against primary isolates of HIV-1. J Immunol 173(1):515–520

    CAS  PubMed  Google Scholar 

  • Wang W, Mulakala C, Ward SC, Jung G, Luong H, Pham D, Waring AJ, Kaznessis Y, Lu W, Bradley KA, Lehrer RI (2006) Retrocyclins kill bacilli and germinating spores of Bacillus anthracis and inactivate anthrax lethal toxin. J Biol Chem 281(43):32755–32764

    CAS  PubMed  Google Scholar 

  • Wehkamp J, Harder J, Weichenthal M, Schwab M, Schäffeler E, Schlee M, Herrlinger KR, Stallmach A, Noack F, Fritz P, Schröder JM, Bevins CL, Fellermann K, Stange EF (2004) NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 53(11):1658–1664

    CAS  PubMed  Google Scholar 

  • Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249(4975):1431–1433

    CAS  PubMed  Google Scholar 

  • Wu Z, Hoover DM, Yang D, Boulègue C, Santamaria F, Oppenheim JJ, Lubkowski J, Lu W (2003) Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human beta-defensin 3. Proc Natl Acad Sci USA 100(15):8880–8885

    CAS  PubMed  Google Scholar 

  • Wu M, McClellan SA, Barrett RP, Hazlett LD (2009a) Beta-defensin-2 promotes resistance against infection with P. aeruginosa. J Immunol 182(3):1609–1616

    CAS  PubMed  Google Scholar 

  • Wu M, McClellan SA, Barrett RP, Zhang Y, Hazlett LD (2009b) Beta-defensins 2 and 3 together promote resistance to Pseudomonas aeruginosa keratitis. J Immunol 183(12):8054–8060

    CAS  PubMed  Google Scholar 

  • Yamamoto-Furusho JK, Barnich N, Hisamatsu T, Podolsky DK (2010) MDP-NOD2 stimulation induces HNP-1 secretion, which contributes to NOD2 antibacterial function. Inflamm Bowel Dis 16(5):736–742

    PubMed  Google Scholar 

  • Yang D, Chertov O, Oppenheim JJ (2001) Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37). J Leuk Biol 69:691–697

    CAS  Google Scholar 

  • Yang D, Biragyn A, Kwak LW, Oppenheim JJ (2002) Mammalian defensins in immunity: more than just microbicidal. Trends Immunol 23(6):291–296

    CAS  PubMed  Google Scholar 

  • Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ (2004) Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 22:181–215

    PubMed  Google Scholar 

  • Yasin B, Wang W, Pang M, Cheshenko N, Hong T, Waring AJ, Herold BC, Wagar EA, Lehrer RI (2004) Theta defensins protect cells from infection by herpes simplex virus by inhibiting viral adhesion and entry. J Virol 78(10):5147–5156

    CAS  PubMed  Google Scholar 

  • Zaalouk TK, Bajaj-Elliott M, George JT, McDonald V (2004) Differential regulation of beta-defensin gene expression during Cryptosporidium parvum infection. Infect Immun 72(5):2772–2779

    CAS  PubMed  Google Scholar 

  • Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 75(1):39–48

    PubMed  Google Scholar 

  • Zhou L, Huang LQ, Beuerman RW, Grigg ME, Li SF, Chew FT, Ang L, Stern ME, Tan D (2004) Proteomic analysis of human tears: defensin expression after ocular surface surgery. J Proteome Res 3(3):410–416

    CAS  PubMed  Google Scholar 

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  1. Anatomy/Cell Biology, Wayne State University, 540 E. Canfield Ave, Detroit, MI, 48201, USA

    Linda Hazlett & Minhao Wu

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  1. Linda Hazlett
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  2. Minhao Wu
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Correspondence to Linda Hazlett.

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Hazlett, L., Wu, M. Defensins in innate immunity. Cell Tissue Res 343, 175–188 (2011). https://doi.org/10.1007/s00441-010-1022-4

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  • DOI: https://doi.org/10.1007/s00441-010-1022-4

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