Enteric alpha defensins in norm and pathology

Annals of Clinical Microbiology and Antimicrobials

Volumn 11, Issue , 2012, Pages

  Lisitsyn, Nikolai A ^a   Bukurova, Yulia A ^a   Nikitina, Inna G ^a   Krasnov, George S ^a   Sykulev, Yuri ^b   Beresten, Sergey F ^a  

^a ENGELHARDT INSTITUTE OF MOLECULAR BIOLOGY   (Russian Federation)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

Colon cancer; Enteric alpha defensins; Ibd; Innate immunity; Paneth cells

Indexed keywords

ALPHA DEFENSIN;

BACTERIUM DETECTION; CELL STRUCTURE; COLON CANCER; ENTERITIS; GENE EXPRESSION; GENE FUNCTION; GENE SEQUENCE; IMMUNITY; INTESTINE; INTESTINE EPITHELIUM; NONHUMAN; PATHOLOGY; PROTEIN PROCESSING; REVIEW; SIGNAL TRANSDUCTION; ULCERATIVE COLITIS; ANIMAL; GASTROINTESTINAL TRACT; HUMAN; IMMUNOLOGY; MAMMAL; PATHOPHYSIOLOGY; PHYSIOLOGY; SECRETION;

ALPHA-DEFENSINS; ANIMALS; ENTERITIS; GASTROINTESTINAL TRACT; HUMANS; MAMMALS;

EID: 84855598096     PISSN: None     EISSN: 14760711     Source Type: Journal    
DOI: 10.1186/1476-0711-11-1     Document Type: Review

References (62)

1. Droin N, Hendra JB, Ducoroy P, Solary E. Human defensins as cancer biomarkers and antitumour molecules. J Proteomics 2009, 72:918-27. 10.1016/j.jprot.2009.01.002, 19186224.
2. Epand RM, Vogel HJ. Diversity of antimicrobial peptides and their mechanisms of action. Biochim Biophys Acta 1999, 1462:11-28. 10.1016/S0005-2736(99)00198-4, 10590300.
3. Lai Y, Gallo RL. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 2009, 30:131-41. 10.1016/j.it.2008.12.003, 2765035, 19217824.
4. Guani-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Teran LM. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol 2010, 135:1-11. 10.1016/j.clim.2009.12.004, 20116332.
5. Salzman NH, Underwood MA, Bevins CL. Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol 2007, 19:70-83. 10.1016/j.smim.2007.04.002, 17485224.
6. Semple CA, Gautier P, Taylor K, Dorin JR. The changing of the guard: Molecular diversity and rapid evolution of beta-defensins. Mol Divers 2006, 10:575-84. 10.1007/s11030-006-9031-7, 16969721.
7. Bauer F, Schweimer K, Kluver E, Conejo-Garcia JR, Forssmann WG, Rosch P, Adermann K, Sticht H. Structure determination of human and murine beta-defensins reveals structural conservation in the absence of significant sequence similarity. Protein Sci 2001, 10:2470-9. 10.1110/ps.ps.24401, 2374044, 11714914.
8. Garcia AE, Osapay G, Tran PA, Yuan J, Selsted ME. Isolation, synthesis, and antimicrobial activities of naturally occurring theta-defensin isoforms from baboon leukocytes. Infect Immun 2008, 76:5883-91. 10.1128/IAI.01100-08, 2583559, 18852242.
9. Szyk A, Wu Z, Tucker K, Yang D, Lu W, Lubkowski J. Crystal structures of human alpha-defensins HNP4, HD5, and HD6. Protein Sci 2006, 15:2749-60. 10.1110/ps.062336606, 2242434, 17088326.
10. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003, 3:710-20. 10.1038/nri1180, 12949495.
11. Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, Buchner J, Schaller M, Stange EF, Wehkamp J. Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 2011, 469:419-23. 10.1038/nature09674, 21248850.
12. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 2000, 1:113-8. 10.1038/77783, 11248802.
13. Chang TL, Klotman ME. Defensins: natural anti-HIV peptides. AIDS reviews 2004, 6:161-8.
14. Zeya HI, Spitznagel JK. Antimicrobial specificity of leukocyte lysosomal cationic proteins. Science 1966, 154:1049-51. 10.1126/science.154.3752.1049, 4958495.
15. Linzmeier RM, Ganz T. Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23. Genomics 2005, 86:423-30. 10.1016/j.ygeno.2005.06.003, 16039093.
16. Wehkamp J, Chu H, Shen B, Feathers RW, Kays RJ, Lee SK, Bevins CL. Paneth cell antimicrobial peptides: topographical distribution and quantification in human gastrointestinal tissues. FEBS Lett 2006, 580:5344-50. 10.1016/j.febslet.2006.08.083, 16989824.
17. Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC. Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 1998, 152:1247-58. 1858596, 9588893.
18. Eisenhauer PB, Lehrer RI. Mouse neutrophils lack defensins. Infect Immun 1992, 60:3446-7. 257335, 1639513.
19. Amid C, Rehaume LM, Brown KL, Gilbert JG, Dougan G, Hancock RE, Harrow JL. Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome. BMC Genomics 2009, 10:606. 10.1186/1471-2164-10-606, 2807441, 20003482.
20. Ouellette AJ, Darmoul D, Tran D, Huttner KM, Yuan J, Selsted ME. Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin. Infect Immun 1999, 67:6643-51. 97078, 10569786.
21. Huttner KM, Selsted ME, Ouellette AJ. Structure and diversity of the murine cryptdin gene family. Genomics 1994, 19:448-53. 10.1006/geno.1994.1093, 8188287.
22. Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003, 422:522-6. 10.1038/nature01520, 12660734.
23. Inoue R, Tsuruta T, Nojima I, Nakayama K, Tsukahara T, Yajima T. Postnatal changes in the expression of genes for cryptdins 1-6 and the role of luminal bacteria in cryptdin gene expression in mouse small intestine. FEMS Immunol Med Microbiol 2008, 52:407-16. 10.1111/j.1574-695X.2008.00390.x, 18328077.
24. Karlsson J, Putsep K, Chu H, Kays RJ, Bevins CL, Andersson M. Regional variations in Paneth cell antimicrobial peptide expression along the mouse intestinal tract. BMC Immunol 2008, 9:37. 10.1186/1471-2172-9-37, 2488317, 18637162.
25. Kelly P, Feakins R, Domizio P, Murphy J, Bevins C, Wilson J, McPhail G, Poulsom R, Dhaliwal W. Paneth cell granule depletion in the human small intestine under infective and nutritional stress. Clin Exp Immunol 2004, 135:303-9. 10.1111/j.1365-2249.2004.02374.x, 1808949, 14738460.
26. Rajabi M, de Leeuw E, Pazgier M, Li J, Lubkowski J, Lu W. The conserved salt bridge in human alpha-defensin 5 is required for its precursor processing and proteolytic stability. The Journal of biological chemistry 2008, 283:21509-18. 10.1074/jbc.M801851200, 2490794, 18499668.
27. Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 2002, 3:583-90. 10.1038/ni797, 12021776.
28. Elphick D, Liddell S, Mahida YR. Impaired luminal processing of human defensin-5 in Crohn's disease: persistence in a complex with chymotrypsinogen and trypsin. Am J Pathol 2008, 172:702-13. 10.2353/ajpath.2008.070755, 2258249, 18258845.
29. Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999, 286:113-7. 10.1126/science.286.5437.113, 10506557.
30. Simons BD, Clevers H. Stem cell self-renewal in intestinal crypt. Exp Cell Res 2011, 317:2719-24. 10.1016/j.yexcr.2011.07.010, 21787769.
31. Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, de Sauvage FJ. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 2011, 7368:255-9.
32. Takeda N, Jain R, Leboeuf MR, Wang Q, Lu MM, Epstein JA. Interconversion Between Intestinal Stem Cell Populations in Distinct Niches. Science 2011,
33. Roberts CL, Keita AV, Duncan SH, O'Kennedy N, Söderholm JD, Rhodes JM, Campbell BJ. Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers. Gut 2010, 59:1331-9. 10.1136/gut.2009.195370, 2976079, 20813719.
34. Gerbe F, van Es JH, Makrini L, Brulin B, Mellitzer G, Robine S, Romagnolo B, Shroyer NF, Bourgaux JF, Pignodel C, et al. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. J Cell Biol 2011, 192:767-80. 10.1083/jcb.201010127, 3051826, 21383077.
35. Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjoberg J, Amir E, Teggatz P, Barman M, Hayward M, Eastwood D, et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 2010, 11:76-83. 10.1038/ni.1825, 2795796, 19855381.
36. Uematsu S, Fujimoto K. The innate immune system in the intestine. Microbiol Immunol 2010, 54:645-57. 10.1111/j.1348-0421.2010.00267.x, 21044138.
37. Choi YJ, Im E, Chung HK, Pothoulakis C, Rhee SH. TRIF mediates Toll-like receptor 5-induced signaling in intestinal epithelial cells. The Journal of biological chemistry 2010, 285:37570-8. 10.1074/jbc.M110.158394, 2988362, 20855887.
38. Foureau DM, Mielcarz DW, Menard LC, Schulthess J, Werts C, Vasseur V, Ryffel B, Kasper LH, Buzoni-Gatel D. TLR9-dependent induction of intestinal alpha-defensins by Toxoplasma gondii. J Immunol 2010, 184:7022-9. 10.4049/jimmunol.0901642, 20488791.
39. Eckmann L. Innate immunity and mucosal bacterial interactions in the intestine. Curr Opin Gastroenterol 2004, 20:82-8. 10.1097/00001574-200403000-00006, 15703626.
40. Menendez A, Ferreira RB, Finlay BB. Defensins keep the peace too. Nat Immunol 2010, 11:49-50. 10.1038/ni0110-49, 20016512.
41. Lin PW, Simon PO, Gewirtz AT, Neish AS, Ouellette AJ, Madara JL, Lencer WI. Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response. The Journal of biological chemistry 2004, 279:19902-7. 10.1074/jbc.M311821200, 14990585.
42. de Leeuw E, Burks SR, Li X, Kao JP, Lu W. Structure-dependent functional properties of human defensin 5. FEBS Lett 2007, 581:515-20. 10.1016/j.febslet.2006.12.036, 1832120, 17250830.
43. Ishikawa C, Tanabe H, Maemoto A, Ito T, Watari J, Kono T, Fujiya M, Ashida T, Ayabe T, Kohgo Y. Precursor processing of human defensin-5 is essential to the multiple functions in vitro and in vivo. J Innate Immun 2009, 2:66-76.
44. Grigat J, Soruri A, Forssmann U, Riggert J, Zwirner J. Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family. J Immunol 2007, 179:3958-65.
45. Lencer WI, Cheung G, Strohmeier GR, Currie MG, Ouellette AJ, Selsted ME, Madara JL. Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3. Proc Natl Acad Sci USA 1997, 94:8585-9. 10.1073/pnas.94.16.8585, 23028, 9238020.
46. Shi J, Aono S, Lu W, Ouellette AJ, Hu X, Ji Y, Wang L, Lenz S, van Ginkel FW, Liles M, et al. A novel role for defensins in intestinal homeostasis: regulation of IL-1beta secretion. J Immunol 2007, 179:1245-53.
47. Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V, Rao AS, Madara JL. Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science 2000, 289:1560-3. 10.1126/science.289.5484.1560, 10968793.
48. Salzman NH, Chou MM, de Jong H, Liu L, Porter EM, Paterson Y. Enteric salmonella infection inhibits Paneth cell antimicrobial peptide expression. Infect Immun 2003, 71:1109-15. 10.1128/IAI.71.3.1109-1115.2003, 148886, 12595421.
49. Xavier RJ, Podolsky DK. Microbiology. How to get along--friendly microbes in a hostile world. Science 2000, 289:1483-4. 10.1126/science.289.5484.1483, 10991734.
50. Negroni A, Stronati L, Pierdomenico M, Tirindelli D, Di Nardo G, Mancini V, Maiella G, Cucchiara S. Activation of NOD2-mediated intestinal pathway in a pediatric population with Crohn's disease. Inflamm Bowel Dis 2009, 15:1145-54. 10.1002/ibd.20907, 19266573.
51. Wehkamp J, Stange EF. A new look at Crohn's disease: breakdown of the mucosal antibacterial defense. Ann N Y Acad Sci 2006, 1072:321-31. 10.1196/annals.1326.030, 17057212.
52. Ramasundara M, Leach ST, Lemberg DA, Day AS. Defensins and inflammation: the role of defensins in inflammatory bowel disease. J Gastroenterol Hepatol 2009, 24:202-8. 10.1111/j.1440-1746.2008.05772.x, 19215333.
53. Rehman A, Sina C, Gavrilova O, Hasler R, Ott S, Baines JF, Schreiber S, Rosenstiel P. Nod2 is essential for temporal development of intestinal microbial communities. Gut 2011, 60:1354-62. 10.1136/gut.2010.216259, 21421666.
54. Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, et al. Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci USA 2005, 102:18129-34. 10.1073/pnas.0505256102, 1306791, 16330776.
55. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005, 307:731-4. 10.1126/science.1104911, 15692051.
56. Wehkamp J, Wang G, Kübler I, Nuding S, Gregorieff A, Schnabel A, Kays RJ, Fellermann K, Burk O, Schwab M, et al. The Paneth cell alpha-defensin deficiency of ileal Crohn's disease is linked to Wnt/Tcf-4. J Immunol 2007, 179:3109-18.
57. Thomson JM, Hansen R, Berry SH, Hope ME, Murray GI, Mukhopadhya I, McLean MH, Shen Z, Fox JG, El-Omar E, et al. Enterohepatic helicobacter in ulcerative colitis: potential pathogenic entities?. PloS one 2011, 6:e17184. 10.1371/journal.pone.0017184, 3044171, 21383845.
58. Stronati L, Negroni A, Pierdomenico M, D'Ottavio C, Tirindelli D, Di Nardo G, Oliva S, Viola F, Cucchiara S. Altered expression of innate immunity genes in different intestinal sites of children with ulcerative colitis. Dig Liver Dis 2010, 42:848-53. 10.1016/j.dld.2010.04.003, 20452301.
59. Quante M, Wang TC. Inflammation and stem cells in gastrointestinal carcinogenesis. Physiology (Bethesda) 2008, 23:350-9.
60. Andreu P, Colnot S, Godard C, Gad S, Chafey P, Niwa-Kawakita M, Laurent-Puig P, Kahn A, Robine S, Perret C, et al. Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development 2005, 132:1443-51. 10.1242/dev.01700, 15716339.
61. Joo M, Shahsafaei A, Odze RD. Paneth cell differentiation in colonic epithelial neoplasms: evidence for the role of the Apc/beta-catenin/Tcf pathway. Hum Pathol 2009, 40:872-80. 10.1016/j.humpath.2008.12.003, 19269007.
62. Radeva MY, Jahns F, Wilhelm A, Glei M, Settmacher U, Greulich KO, Mothes H. Defensin alpha 6 (DEFA 6) overexpression threshold of over 60 fold can distinguish between adenoma and fully blown colon carcinoma in individual patients. BMC Cancer 2010, 10:588. 10.1186/1471-2407-10-588, 2984430, 20979654.