Abstract
Host defense responses of the human female genital tract mucosa to pathogenic microbes and viruses are mediated in part by the release of antimicrobial substances into the overlying mucosal fluid. While host defense has long been considered a prominent function of vaginal and cervical mucosae, evidence that cationic antimicrobial peptides and proteins have fundamental roles in the innate host defense of this tissue has only recently become available. This chapter explores elements of the physical and chemical defense barriers of the cervicovaginal mucosa, which protect against infections of the lower genital tract. Cationic antimicrobial and antiviral polypeptide components of cervicovaginal fluid are discussed in detail, with special emphasis placed on the defensin family of peptides as well as polypeptides that are active against viruses such as HIV-1. The reader should be cognizant that each polypeptide by itself does not provide complete protection of the genital tract. On the contrary, the abundance and multiplicity of antimicrobial peptides and proteins suggest protection of the cervicovaginal mucosa may be best realized from the aggregate effector molecules.
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References
Abuja PM, Zenz A, Trabi M, Craik DJ, Lohner K (2004) The cyclic antimicrobial peptide RTD-1 induces stabilized lipid-peptide domains more efficiently than its open-chain analogue. FEBS Lett 566:301–306
Agerberth B, Gunne H, Odeberg J, Kogner P, Boman HG, Gudmundsson GH (1995) FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proc Natl Acad Sci U S A 92:195–199
Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jornvall 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 96:3086–3093
Agnew KJ, Hillier SL (1995) The effect of treatment regimens for vaginitis and cervicitis on vaginal colonization by lactobacilli. Sex Transm Dis 22:269–273
Aho HJ, Grenman R, Sipila J, Peuravuori H, Hartikainen J, Nevalainen TJ (1997) Group II phospholipase A2 in nasal fluid, mucosa and paranasal sinuses. Acta Otolaryngol (Stockh) 117:860–863
Alcouloumre MS, Ghannoum MA, Ibrahim AS, Selsted ME, Edwards JEJ (1993) Fungicidal properties of defensin NP-1 and activity against Cryptococcus neoformans in vitro. Antimicrob Agents Chemother 37:2628–2632
Aley SB, Zimmerman M, Hetsko M, Selsted ME, Gillin FD (1994) Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides. Infect Immun 62:5397–5403
Andersen JH, Osbakk SA, Vorland LH, Traavik T, Gutteberg TJ (2001) Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts. Antiviral Res 51:141–149
Arnold RR, Russell JE, Champion WJ, Brewer M, Gauthier JJ (1982) Bactericidal activity of human lactoferrin: differentiation from the stasis of iron deprivation. Infect Immun 35:792–799
Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, Gurguis A, Faro S (2001) Defense factors of vaginal lactobacilli. Am J Obstet Gynecol 185:375–379
Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ (2000) Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 1:113–118
Bals R (2000) Epithelial antimicrobial peptides in host defense against infection. Respir Res 1:141–150
Bals R, Wang X, Zasloff M, Wilson JM (1998) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci U S A 95:9541–9546
Balu RB, Savitz DA, Ananth CV, Hartmann KE, Miller WC, Thorp JM, Heine RP (2002) Bacterial vaginosis and vaginal fluid defensins during pregnancy. Am J Obstet Gynecol 187:1267–1271
Balu RB, Savitz DA, Ananth CV, Hartmann KE, Miller WC, Thorp JM, Heine RP (2003) Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. Obstet Gynecol 101:862–868
Barousse MM, Steele C, Dunlap K, Espinosa T, Boikov D, Sobel JD, Fidel PL Jr (2001) Growth inhibition of Candida albicans by human vaginal epithelial cells. J Infect Dis 184:1489–1493
Becker MN, Diamond G, Verghese MW, Randell SH (2000) CD14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human tracheobronchial epithelium. J Biol Chem 275:29731–29736
Bellamy W, Takase M, Wakabayashi H, Kawase K, Tomita M (1992) Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the Nterminal region of bovine lactoferrin. J Appl Bacteriol 73:472–479
Bensch KW, Raida M, Magert HJ, Schulz-Knappe P, Forssmann WG (1995) hBD-1: a novel beta-defensin from human plasma. FEBS Lett 368:331–335
Bevins CL (2004) The Paneth cell and the innate immune response. Curr Opin Gastroenterol 20:572–580
Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW (2002) Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298:1025–1029
Birchler T, Seibl R, Buchner K, Loeliger S, Seger R, Hossle JP, Aguzzi A, Lauener RP (2001) Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein. Eur J Immunol 31:3131–3137
Brandtzaeg P, Gabrielsen TO, Dale I, Muller F, Steinbakk M, Fagerhol MK (1995) The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at epithelial surfaces. Adv Exp Med Biol 371A:201–206
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535
Brown D Jr (2004) Clinical variability of bacterial vaginosis and trichomoniasis. J Reprod Med 49:781–786
Brunham RC, Rey-Ladino J (2005) Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine. Nat Rev Immunol 5:149–161
Bullen JJ, Armstrong JA (1979) The role of lactoferrin in the bactericidal function of polymorphonuclear leucocytes. Immunology 36:781–791
Cates W Jr (1999) Estimates of the incidence and prevalence of sexually transmitted diseases in the United States. American Social Health Association Panel. Sex Transm Dis 26: S2–S7
Chang JH, Ryang YS, Morio T, Lee SK, Chang EJ (2004) Trichomonas vaginalis inhibits proinflammatory cytokine production in macrophages by suppressing NF-kappaB activation. Mol Cells 18:177–185
Chang TL, Francois F, Mosoian A, Klotman ME (2003) CAF-mediated human immunodeficiency virus (HIV) type 1 transcriptional inhibition is distinct from alpha-defensin-1 HIV inhibition. J Virol 77:6777–6784
Chang TL, Vargas J Jr, DelPortillo A, Klotman ME (2005) Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 115:765–773
Chapple DS, Joannou CL, Mason DJ, Shergill JK, Odell EW, Gant V, Evans RW (1998) A helical region on human lactoferrin. Its role in antibacterial pathogenesis. Adv Exp Med Biol 443:215–220
Chen FY, Lee MT, Huang HW (2003) Evidence for membrane thinning effect as the mechanism for peptide-induced pore formation. Biophys J 84:3751–3758
Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL (2003) Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis 37:319–325
Chimura T, Hirayama T, Takase M (1993) Lysozyme in cervicalmucus of patients with chorioamnionitis. Jpn J Antibiot 46:726–729
Cibley LJ, Cibley LJ (1991) Cytolytic vaginosis. Am J Obstet Gynecol 165:1245–1249
Clohessy PA, Golden BE (1996) Themechanism of calprotectin’s candidastatic activity appears to involve zinc chelation. Biochem Soc Trans 24:309S
Cole AM, Dewan P, Ganz T (1999) Innate antimicrobial activity of nasal secretions. Infect Immun 67:3267–3275
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 U S A 99:1813–1818
Cowland JB, Johnsen AH, Borregaard N (1995) hCAP-18, a cathelin/pro-bactenecinlike protein of human neutrophil specific granules. FEBS Lett 368:173–176
Daher KA, Selsted ME, Lehrer RI (1986) Direct inactivation of viruses by human granulocyte defensins. J Virol 60:1068–1074
Diamond G, Zasloff M, Eck H, Brasseur M, Maloy WL, Bevins CL (1991) Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A 88:3952–3956
Draper DL, Landers DV, Krohn MA, Hillier SL, Wiesenfeld HC, Heine RP (2000) Levels of vaginal secretory leukocyte protease inhibitor are decreased in women with lower reproductive tract infections. Am J Obstet Gynecol 183:1243–1248
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 106:517–525
Duits LA, Nibbering PH, van Strijen E, Vos JB, Mannesse-Lazeroms SP, van Sterkenburg MA, Hiemstra PS (2003) Rhinovirus increases human beta-defensin-2 and-3 mRNA expression in cultured bronchial epithelial cells. FEMS Immunol Med Microbiol 38:59–64
Edwards JL, Apicella MA (2004) The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin Microbiol Rev 17:965–981
Edwards L (2004) The diagnosis and treatment of infectious vaginitis. Dermatol Ther 17:102–110
Ellison RT3, Giehl TJ (1991) Killing of Gram-negative bacteria by lactoferrin and lysozyme. J Clin Invest 88:1080–1091
Faurschou M, Kamp S, Cowland JB, Udby L, Johnsen AH, Calafat J, Winther H, Borregaard N (2005) Prodefensins are matrix proteins of specific granules in human neutrophils. J Leukoc Biol 78:785–793
Fidel PL Jr (2004) History and new insights into host defense against vaginal candidiasis. Trends Microbiol 12:220–227
Fidel PL Jr (2005) Immunity in vaginal candidiasis. Curr Opin Infect Dis 18:107–111
Fidel PL Jr, Barousse M, Espinosa T, Ficarra M, Sturtevant J, Martin DH, Quayle AJ, Dunlap K (2004) An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis. Infect Immun 72:2939–2946
Fleming A (1922) On a remarkable bacteriolytic element found in tissues and secretions. Proc R Soc Lond [Biol] 93:306–317
Frohm NM, Sandstedt B, Sorensen O, Weber G, Borregaard N, Stahle-Backdahl M (1999) The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6. Infect Immun 67:2561–2566
Ganz T (1999) Defensins and host defense. Science 286:420–421
Ganz T (2001) Defensins in the urinary tract and other tissues. J Infect Dis 183[Suppl 1]:S41–S42
Ganz T (2005) Defensins and other antimicrobial peptides: a historical perspective and an update. Comb Chem High Throughput Screen 8:209–217
Ganz T, Lehrer RI (1994) Defensins. Curr Opin Immunol 6:584–589
Ganz T, Lehrer RI (1997) Antimicrobial peptides of leukocytes. Curr Opin Hematol 4:53–58
Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76:1427–1435
Gazit E, Miller IR, Biggin PC, Sansom MS, Shai Y (1996) Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. J Mol Biol 258:860–870
Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL (2002) Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 3:583–590
Ghosh SK, Zhao J, Philogene MC, Alzaharani A, Rane S, Banerjee A (2004) Pathogenic consequences of Neisseria gonorrhoeae pilin glycan variation. Microbes Infect 6:693–701
Grouard G, Clark EA (1997) Role of dendritic and follicular dendritic cells in HIV infection and pathogenesis. Curr Opin Immunol 9:563–567
Harder J, Bartels J, Christophers E, Schroeder J-M (1997) A peptide antibiotic from human skin. Nature 387:861–862
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 276:5707–5713
Harmsen MC, Swart PJ, de Bethune MP, Pauwels R, De Clercq E, The TH, Meijer DK (1995) Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J Infect Dis 172:380–388
Harwig SS, Park AS, Lehrer RI (1992) Characterization of defensin precursors in mature human neutrophils. Blood 79:1532–1537
Hasegawa K, Motsuchi W, Tanaka S, Dosako S (1994) Inhibition with lactoferrin of in vitro infection with human herpes virus. Jpn J Med Sci Biol 47:73–85
Hashemi FB, Mollenhauer J, Madsen LD, Sha BE, Nacken W, Moyer MB, Sorg C, Spear GT (2001) Myeloid-related protein (MRP)-8 from cervico-vaginal secretions activates HIV replication. AIDS 15:441–449
Hein M, Valore EV, Helmig RB, Uldbjerg N, Ganz T (2002) Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol 187:137–144
Helmig R, Uldbjerg N, Ohlsson K (1995) Secretory leukocyte protease inhibitor in the cervical mucus and in the fetal membranes. Eur J Obstet Gynecol Reprod Biol 59:95–101
Hertz CJ, Wu Q, Porter EM, Zhang YJ, Weismuller KH, Godowski PJ, Ganz T, Randell SH, Modlin RL (2003) Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J Immunol 171:6820–6826
Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, Dijkman JH (1996) Antibacterial activity of antileukoprotease. Infect Immun 64:4520–4524
Hillier SL (1999) Normal vaginal flora. In: Holmes KK et al (eds) Sexually transmitted diseases. McGraw-Hill, New York, pp 191–204
Hirsch JG (1958) Bactericidal action of histone. J Exp Med 108:925–944
Hobbs JA, May R, Tanousis K, McNeill E, Mathies M, Gebhardt C, Henderson R, Robinson MJ, Hogg N (2003) Myeloid cell function in MRP-14 (S100A9) null mice. Mol Cell Biol 23:2564–2576
Horowitz BJ, Mardh PA, Nagy E, Rank EL (1994) Vaginal lactobacillosis. Am J Obstet Gynecol 170:857–861
Hughes AL (1999) Evolutionary diversification of the mammalian defensins. Cell Mol Life Sci 56:94–103
Ibrahim HR, Matsuzaki T, Aoki T (2001) Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function. FEBS Lett 506:27–32
Joiner KA, Ganz T, Albert J, Rotrosen D (1989) The opsonizing ligand on Salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes. J Cell Biol 109:2771–2782
Jones DE, Bevins CL (1992) Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 267:23216–23225
Jones DE, Bevins CL (1993) Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the humanbowel. FEBS Lett 315:187–192
Kossel A (1896) Uber die basichen Stoffe des Zellkerns. Z Ohysiol Chem 22:176–190
Laible NJ, Germaine GR (1985) Bactericidal activity of human lysozyme, muramidase-inactive lysozyme, and cationic polypeptides against Streptococcus sanguis and Streptococcus faecalis: inhibition by chitin oligosaccharides. Infect Immun 48:720–728
Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC (1995) Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 63:1291–1297
Lee-Huang S, Huang PL, Sun Y, Huang PL, Kung HF, Blithe DL, Chen HC (1999) Lysozyme and RNases as anti-HIV components in beta-core preparations of human chorionic gonadotropin. Proc Natl Acad Sci U S A 96:2678–2681
Lee-Huang S, Maiorov V, Huang PL, Ng A, Lee HC, Chang YT, Kallenbach N, Huang PL, Chen HC (2005) Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity. Biochemistry 44:4648–4655
Lehrer RI, Ganz T (2002) Defensins of vertebrate animals. Curr Opin Immunol 14:96–102
Lehrer RI, Daher K, Ganz T, Selsted ME (1985a) Direct inactivation of viruses by MCP-1 and MCP-2, natural peptide antibiotics from rabbit leukocytes. J Virol 54:467–472
Lehrer RI, Szklarek D, Ganz T, Selsted ME (1985b) Correlation of binding of rabbit granulocyte peptides to Candida albicans with candidacidal activity. Infect Immun 49:207–211
Lehrer RI, Ganz T, Szklarek D, Selsted ME (1988) Modulation of the in vitro candidacidal activity of human neutrophil defensins by target cell metabolism and divalent cations. J Clin Invest 81:1829–1835
Lehrer RI, Bevins CL, Ganz T (1999) Defensins and other antimicrobial peptides. In: Ogra PL, Mestecky J, Lamm ME, Strober W, Bienenstock J, McGhee JR (eds) Mucosal immunology. Academic Press, San Diego, pp 89–99
Leonova L, Kokryakov VN, Aleshina GM, Hong T, Nguyen T, Zhao C, Waring AJ, Lehrer RI (2001) Circular minidefensins and posttranslational generation of molecular diversity. J Leukoc Biol 70:461–464
Liu L, Zhao C, Heng HHQ, Ganz T (1997) The human β-defensin-1 and α-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry. Genomics 43:316–32
Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728
Mackewicz CE, Yuan J, Tran P, Diaz L, Mack E, Selsted ME, Levy JA (2003) Alphadefensins can have anti-HIV activity but are not CD8 cell anti-HIV factors. AIDS 17:F23–F32
Mangoni ME, Aumelas A, Charnet P, Roumestand C, Chiche L, Despaux E, Grassy G, Calas B, Chavanieu A (1996) Change inmembrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation. FEBS Lett 383:93–98
Manitz MP, Horst B, Seeliger S, Strey A, Skryabin BV, Gunzer M, Frings W, Schonlau F, Roth J, Sorg C, Nacken W (2003) Loss of S100A9 (MRP14) Results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. Mol Cell Biol 23:1034–1043
Matsuzaki K (2001) Why and how are peptide-lipid interactions utilized for self defence? Biochem Soc Trans 29:598–601
McCray PB, Bentley L (1997) Human airway epithelia express a β-defensin. Am J Respir Cell Mol Biol 16:343–349
McGregor JA, French JI (2000) Bacterial vaginosis in pregnancy. Obstet Gynecol Surv 55:S1–S19
McNeely TB, Dealy M, Dripps DJ, Orenstein JM, Eisenberg SP, Wahl SM (1995) Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro. J Clin Invest 96:456–464
McNeely TB, Shugars DC, Rosendahl M, Tucker C, Eisenberg SP, Wahl SM (1997) Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription. Blood 90:1141–1149
Meredith SD, Raphael GD, Baraniuk JN, Banks SM, Kaliner MA (1989) The pathophysiology of rhinitis. III. The control of IgG secretion. J Allergy Clin Immunol 84:920–930
Miller BF, Abrams R, Dorfman A, Klein M (1942) Antibacterial properties of protamine and histone. Science 96:428–430
Monell CR, Strand M (1994) Structural and functional similarities between synthetic HIV gp41 peptides and defensins. Clin Immunol Immunopathol 71:315–324
Morrison GM, Davidson DJ, Dorin JR (1999) A novel mouse beta defensin, Defb2, which is upregulated in the airways by lipopolysaccharide. FEBS Lett 442:112–116
Münk 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 19:875–881
Nakashima H, Yamamoto N, Masuda M, Fujii N (1993) Defensins inhibit HIV replication in vitro (letter). AIDS 7:1129
Negroni P, Fischer I (1944) Antibiotic action of protamines and histones. Rev Soc Argentina Biol 20:307–314
Nguyen TX, Cole AM, Lehrer RI (2003) Evolution of primate theta-defensins: a serpentine path to a sweet tooth. Peptides 24:1647–1654
Niyonsaba F, Iwabuchi K, Matsuda H, Ogawa H, Nagaoka I (2002) Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol 14:421–426
Ogata K, Linzer BA, Zuberi RI, Ganz T, Lehrer RI, Catanzaro A (1992) Activity of defensins from human neutrophilic granulocytes against Mycobacterium avium-Mycobacterium intracellulare. Infect Immun 60:4720–4725
Oren A, Ganz T, Liu L, Meerloo T (2003) In human epidermis, [beta]-defensin 2 is packaged in lamellar bodies. Exp Mol Pathol 74:180–182
Ouellette AJ (2005) Paneth cell alpha-defensins: peptidemediators of innate immunity in the small intestine. Springer Semin Immunopathol 27:133–146
Ouellette AJ, Bevins CL (2001) Paneth cell defensins and innate immunity of the small bowel. Inflamm Bowel Dis 7:43–50
Panyutich A, Ganz T (1991) Activated alpha 2-macroglobulin is a principal defensinbinding protein. Am J Respir Cell Mol Biol 5:101–106
Panyutich AV, Szold O, Poon PH, Tseng Y, Ganz T (1994) Identification of defensin binding to C1 complement. FEBS Lett 356:169–173
Panyutich AV, Hiemstra PS, Van Wetering S, Ganz T (1995) Human neutrophil defensin and serpins form complexes and inactivate each other. Am J Respir Cell Mol Biol 12:351–357
Park CB, Yi KS, Matsuzaki K, Kim MS, Kim SC (2000) Structure-activity analysis of buforin II, a histone H2A-derived antimicrobial peptide: the proline hinge is responsible for the cell-penetrating ability of buforin II. Proc Natl Acad Sci U S A 97:8245–8250
Patterson BK, Landay A, Andersson J, Brown C, Behbahani H, Jiyamapa D, Burki Z, Stanislawski D, Czerniewski MA, Garcia P (1998) Repertoire of chemokine receptor expression in the female genital tract: implications for human immunodeficiency virus transmission. Am J Pathol 153:481–490
Patton DL, Thwin SS, Meier A, Hooton TM, Stapleton AE, Eschenbach DA (2000) Epithelial cell layer thickness and immune cell populations in the normal human vagina at different stages of the menstrual cycle. Am J Obstet Gynecol 183:967–973
Pillay K, Coutsoudis A, Gadzi-Naqvi AK, Kuhn L, Coovadia HM, Janoff EN (2001) Secretory leukocyte protease inhibitor in vaginal fluids and perinatal human immunodeficiency virus type 1 transmission. J Infect Dis 183:653–656
Pivarcsi A, Nagy I, Koreck A, Kis K, Kenderessy-Szabo A, Szell M, Dobozy A, Kemeny L (2005) Microbial compounds induce the expression of pro-inflammatory cytokines, chemokines and human beta-defensin-2 in vaginal epithelial cells. Microbes Infect 7:1117–1127
Puddu P, Borghi P, Gessani S, Valenti P, Belardelli F, Seganti L (1998) Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection. Int J Biochem Cell Biol 30:1055–1062
Qu XD, Lloyd KC, Walsh JH, Lehrer RI (1996) Secretion of type II phospholipase A2 and cryptdin by rat small intestinal Paneth cells. Infect Immun 64:5161–5165
Quayle AJ (2002) The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. J Reprod Immunol 57:61–79
Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC (1998) Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 152:1247–1258
Quinones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, Marotta ML, Mirza M, Jiang B, Kiser P, Medvik K, Sieg SF, Weinberg A (2003) Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS 17: F39–F48
Reid G (2001) Probiotic agents to protect the urogenital tract against infection. Am J Clin Nutr 73:437S–443S
Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL (2003) Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422:522–526
Satoh Y (1988) Effect of live and heat-killed bacteria on the secretory activity of Paneth cells in germ-free mice. Cell Tissue Res 251:87–93
Satoh Y, Ishikawa K, Oomori Y, Takeda S, Ono K (1992) Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells ofmouse intestine. Cell Tissue Res 269:213–220
Schonwetter BS, Stolzenberg ED, Zasloff MA (1995) Epithelial antibiotics induced at sites of inflammation. Science 267:1645–1648
Schwebke JR, Burgess D (2004) Trichomoniasis. Clin Microbiol Rev 17:794–803
Selsted ME, Harwig SS (1987) Purification, primary structure, and antimicrobial activities of a guinea pig neutrophil defensin. Infect Immun 55:2281–2286
Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6:551–557
Selsted ME, Szklarek D, Lehrer RI (1984) Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect Immun 45:150–154
Selsted ME, Tang YQ, Morris WL, McGuire PA, Novotny MJ, Smith W, Henschen AH, Cullor JS (1993) Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. J Biol Chem 268:6641–6648
Shafer WM, Veal WL, Lee EH, Zarantonelli L, Balthazar JT, Rouquette C (2001) Genetic organization and regulation of antimicrobial efflux systems possessed by Neisseria gonorrhoeae and Neisseria meningitidis. J Mol Microbiol Biotechnol 3:219–224
Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipids bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1462:55–70
Shi J, Zhang G, Wu H, Ross C, Blecha F, Ganz T (1999) Porcine epithelial beta-defensin 1 is expressed in the dorsal tongue at antimicrobial concentrations. Infect Immun 67:3121–3127
Shugars DC, Alexander AL, Fu K, Freel SA (1999) Endogenous salivary inhibitors of human immunodeficiency virus. Arch Oral Biol 44:445–453
Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BD, Greenberg EP, Valore EV, Welsh MJ, Ganz T, Tack BF, McCray PBJ (1998) Production of β-defensins by human airway epithelia. Proc Natl Acad Sci U S A 95:14961–14966
Singh PK, Tack BF, McCray PB Jr, Welsh MJ (2000) Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol 279:L799–L805
Sinha S, Cheshenko N, Lehrer RI, Herold BC (2003) NP-1, a rabbit alpha-defensin, prevents the entry and intercellular spread of herpes simplex virus type 2. Antimicrob Agents Chemother 47:494–500
Sobel JD (1992) Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis 14[Suppl 1]:S148–S153
Sobel JD (2004) Current trends and challenges in candidiasis. Oncology (Huntingt) 18:7–8
Sohnle PG, Hunter MJ, Hahn B, Chazin WJ (2000) Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14). J Infect Dis 182:1272–1275
Sorensen OE, Gram L, Johnsen AH, Andersson E, Bangsboll S, Tjabringa GS, Hiemstra PS, Malm J, Egesten A, Borregaard N (2003) Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. J Biol Chem 278:28540–28546
Sorensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T (2005) Differential regulation of beta-defensin expression in human skin by microbial stimuli. J Immunol 174:4870–4879
Steinbakk M, Naess-Andresen CF, Lingaas E, Dale I, Brandtzaeg P, Fagerhol MK (1990) Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet 336:763–765
Steinman RM, Inaba K (1999) Myeloid dendritic cells. J Leukoc Biol 66:205–208
Swart PJ, Kuipers EM, Smit C, Van Der Strate BW, Harmsen MC, Meijer DK (1998) Lactoferrin. Antiviral activity of lactoferrin. Adv Exp Med Biol 443:205–213
Taha TE, Hoover DR, Dallabetta GA, Kumwenda NI, Mtimavalye LA, Yang LP, Liomba GN, Broadhead RL, Chiphangwi JD, Miotti PG (1998) Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 12:1699–1706
Taha TE, Gray RH, Kumwenda NI, Hoover DR, Mtimavalye LA, Liomba GN, Chiphangwi JD, Dallabetta GA, Miotti PG (1999) HIV infection and disturbances of vaginal flora during pregnancy. J Acquir Immune Defic Syndr Hum Retrovirol 20:52–59
Tang YQ, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, Ouellette AJ, Selsted ME (1999) A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated α-defensins. Science 286:498–502
Tomee JF, Koeter GH, Hiemstra PS, Kauffman HF (1998) Secretory leukoprotease inhibitor: a native antimicrobial protein presenting a new therapeutic option? Thorax 53:114–116
Trabi M, Schirra HJ, Craik DJ (2001) Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes. Biochemistry 40:4211–4221
Tran D, Tran PA, Tang YQ, Yuan J, Cole T, Selsted ME (2002) Homodimeric thetadefensins from Rhesus macaque leukocytes—Isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J Biol Chem 277:3079–3084
Turner J, Cho Y, Dinh NN, Waring AJ, Lehrer RI (1998) Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob Agents Chemother 42:2206–2214
Turpin JA, Schaeffer CA, Bu M, Graham L, Buckheit RW Jr, Clanton D, Rice WG (1996) Human immunodeficiency virus type-1 (HIV-1) replication is unaffected by human secretory leukocyte protease inhibitor. Antiviral Res 29:269–277
UNAIDS/World Health Organization (2004) Global estimates of HIV/AIDS epidemic. www unaids org [accessed June 13, 2005]
Valore EV, Ganz T (1992) Posttranslational processing of defensins inimmature human myeloid cells. Blood 79:1538–1544
Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB, Ganz T (1998) Human β-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633–1642
Valore EV, Park CH, Igreti SL, Ganz T (2002) Antimicrobial components of vaginal fluid. Am J Obstet Gynecol 187:561–568
Vaughan VC, Novy FG, McClintock CT (1893) The germicidal properties of nucleins. Med News 62:536–538
Wang SA, Papp JR, Stamm WE, Peeling RW, Martin DH, Holmes KK (2005) Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report. J Infect Dis 191:917–923
Wang W, Cole AM, Hong T, Waring AJ, Lehrer RI (2003) Retrocyclin, an Antiretroviral θ-defensin, is a lectin. J Immunol 170:4708–4716
Wang X, Zhang Z, Louboutin JP, Moser C, Weiner DJ, Wilson JM (2003) Airway epithelia regulate expression of human beta-defensin 2 through Toll-like receptor 2. FASEB J 17:1727–1729
Wang YQ, Griffiths WJ, Jornvall H, Agerberth B, Johansson J (2002) Antibacterial peptides in stimulated human granulocytes—characterization of ubiquitinated histone H1A. Eur J Biochem 269:512–518
Wasserheit JN (1992) Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. Sex Transm Dis 19:61–77
Wecke J, Lahav M, Ginsburg I, Giesbrecht P (1982) Cell wall degradation of Staphylococcus aureus by lysozyme. Arch Microbiol 131:116–123
Weiss TM, Yang L, Ding L, Wang WC, Waring AJ, Lehrer RI, Huang HW (2002) Two states of a cyclic antimicrobial peptide theta-defensin in lipid bilayers. Biophys J 82:7A
Wiesenfeld HC, Hillier SL, Krohn MA, Landers DV, Sweet RL (2003) Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 36:663–668
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 78:5147–5156
Zanetti M, Gennaro R, Romeo D (1995) Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett 374:1–5
Zariffard MR, Harwani S, Novak RM, Graham PJ, Ji X, Spear GT (2004) Trichomonas vaginalis infection activates cells through toll-like receptor 4. Clin Immunol 111:103–107
Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395
Zhang L, He T, Talal A, Wang G, Frankel SS, Ho DD (1998) In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5. J Virol 72:5035–5045
Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, Fu S, Pham T, Mei J, Ho JJ, Zhang W, Lopez P, Ho DD (2002) Contribution of human alpha-defensin-1,-2 and-3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 298:995–1000
Zhao C, Nguyen T, Liu L, Sacco RE, Brogden KA, Lehrer RI (2001) Gallinacin-3, an Inducible Epithelial β-Defensin in the Chicken. Infect Immun 69:2684–2691
Zimmermann GR, Legault P, Selsted ME, Pardi A (1995) Solution structure of bovine neutrophil beta-defensin-12: the peptide fold of the beta-defensins is identical to that of the classical defensins. Biochemistry 34:13663–13671
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Cole, A.M. (2006). Innate Host Defense of Human Vaginal and CervicalMucosae. In: Shafer, W.M. (eds) Antimicrobial Peptides and Human Disease. Current Topics in Microbiology and Immunology, vol 306. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-29916-5_8
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