The Paneth cell and the innate immune response

Current Opinion in Gastroenterology

Volumn 20, Issue 6, 2004, Pages 572-580

  Bevins, Charles L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Innate immune response; Paneth cell

Indexed keywords

ALPHA DEFENSIN; ANGIOGENIN; CRYPTDIN; ENZYME PRECURSOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 8; LYSOZYME; MATRILYSIN; MITOGEN ACTIVATED PROTEIN KINASE P38; PHOSPHOLIPASE A2; PROTEIN; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ANGIOGENESIS; ANTIMICROBIAL ACTIVITY; BACTERIAL COLONIZATION; BACTERIAL VIRULENCE; BACTEROIDES THETAIOTAOMICRON; CELL DIFFERENTIATION; CELL FUNCTION; CROHN DISEASE; CRYPT CELL; CRYPTOSPORIDIOSIS; CYSTIC FIBROSIS; CYTOKINE RELEASE; DISULFIDE BOND; GENE MUTATION; GRAM POSITIVE BACTERIUM; HOST RESISTANCE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; ILEUM; IMMUNITY; IMMUNOCOMPETENT CELL; INFECTION SENSITIVITY; INNATE IMMUNITY; INTESTINE FLORA; INTESTINE VILLUS; LISTERIA MONOCYTOGENES; NECROTIZING ENTEROCOLITIS; NIPPOSTRONGYLUS BRASILIENSIS; NONHUMAN; PANETH CELL; PARASITOSIS; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REAL TIME POLYMERASE CHAIN REACTION; REVIEW; SALMONELLA; SALMONELLA TYPHIMURIUM; SECRETORY GRANULE; SMALL INTESTINE; SMALL INTESTINE MUCOSA; STATISTICAL SIGNIFICANCE; T LYMPHOCYTE; TRICHINELLA SPIRALIS; ZINC DEFICIENCY;

EID: 7444239122     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001574-200411000-00012     Document Type: Review

References (82)

1. Porter EM, Bevins CL, Ghosh D, Ganz T: The multifaceted Paneth cell. Cell Mol Life Sci 2002, 59:156-170.
2. Booth C, Potten CS: Gut instincts: thoughts on intestinal epithelial stem cells. J Clin Invest 2000, 105:1493-1499.
3. Simon GL, Gorbach SL: Normal alimentary tract microflora. In Infections of the Gastrointestinal Tract. Edited by Blaser MJ, Smith PD, Ravdin JI, Greenberg HB, Guerrant RL. New York: Raven Press; 1995:53-69.
4. Hecht G: Innate mechanisms of epithelial host defense: spotlight on intestine. Am J Physiol 1999, 277:C351-C358.
5. Ayabe T, Satchell DP, Wilson CL, et al.: Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 2000, 1:113-118.
6. Ghosh D, Porter EM, Shen B, et al.: Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 2002, 3:583-590.
7. Wilson CL, Ouellette AJ, Satchell DP, et al.: Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999, 286:113-117.
8. Salzman NH, Ghosh D, Huttner KM, et al.: Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 2003, 422:522-526. Strong experimental evidence from an in vivo model for a role of Paneth cell defensins in innate immunity.
9. Ouellette AJ: Defensin-mediated innate immunity in the small intestine. Best Pract Res Clin Gastroenterol 2004, 18:405-419. Excellent review from scientist who discovered Paneth cell defensins.
10. Cunliffe RN, Mahida YR: Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J Leukoc Biol 2004, 75:49-58.
11. Ganz T: Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003, 3:710-720. Well-written review from pioneer in field that will appeal to students and seasoned investigators alike.
12. Ouellette AJ, Cordell B: Accumulation of abundant messenger ribonucleic acids during postnatal development of mouse small intestine. Gastroenterology 1988, 94:114-121.
13. Ouellette AJ, Miller SI, Henschen AH, Selsted ME: Purification and primary structure of murine cryptdin-1, a Paneth cell defensin. FEBS Lett 1992, 304:146-148.
14. Qu XD, Lloyd KC, Walsh JH, Lehrer RI: Secretion of type II phospholipase A2 and cryptdin by rat small intestinal Paneth cells. Infect Immun 1996, 64:5161-5165.
15. Qu XD, Lehrer RI: Secretory phospholipase A2 is the principal bactericide for staphylococci and other gram-positive bacteria in human tears. Infect Immun 1998, 66:2791-2797.
16. Weinrauch Y, Abad C, Liang NS, et al.: Mobilization of potent plasma bactericidal activity during systemic bacterial challenge. Role of group IIA phospholipase A2. J Clin Invest 1998, 102:633-638.
17. Lehrer RI, Bevins CL, Ganz T: Defensins and other antimicrobial peptides. In Mucosal Immunology. 2nd ed. Edited by Ogra PL, Mestecky J, Lamm ME, Strober WM, Bienstock J. 2nd ed. New York: Academic Press; 1998:89-99.
18. Boman HG: Antibacterial peptides: basic facts and emerging concepts. J Intern Med 2003, 254:197-215. Review with new ideas from a scientist who helped found the field of antimicrobial peptides.
19. Zasloff M: Antimicrobial peptides of multicellular organisms. Nature 2002, 415:389-395.
20. Zanetti M, Gennaro R, Scocchi M, Skerlavaj B: Structure and biology of cathelicidins. Adv Exp Med Biol 2000, 479:203-218.
21. Lehrer RI, Ganz T: Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 2002, 9:18-22.
22. Zaiou M, Gallo RL: Cathelicidins, essential gene-encoded mammalian antibiotics. J Mol Med 2002, 80:549-561.
23. Gunn JS, Ryan SS, Ernst RK, Miller SI: Genetic and functional analysis of a PmrA-PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of salmonella enterica serovar typhimurium. Infect Immun 2000, 68:6139-6146.
24. Tamayo R, Ryan SS, McCoy AJ, Gunn JS: Identification and genetic characterization of PmrA-regulated genes and genes involved in polymyxin B resistance in Salmonella enterica serovar typhimurium. Infect Immun 2002, 70:6770-6778.
25. Lee H, Hsu FF, Turk J, Groisman EA: The PmrA-Regulated pmrC Gene Mediates Phosphoethanolamine Modification of Lipid A and Polymyxin Resistance in Salmonella enterica. J Bacteriol 2004, 186:4124-4133.
26. Peschel A: How do bacteria resist human antimicrobial peptides? Trends Microbiol 2002, 10:179-186.
27. Ouellette AJ, Satchell DP, Hsieh MM, et al.: Characterization of luminal Paneth cell alpha-defensins in mouse small intestine: attenuated antimicrobial activities of peptides with truncated amino termini. J Biol Chem 2000, 275:33969-33973.
28. Satchell DP, Sheynis T, Shirafuji Y, et al.: Interactions of mouse paneth cell alpha-defensins and alpha-defensin precursors with membranes: Prosegment inhibition of peptide association with biomimetic membranes. J Biol Chem 2003, 278:13838-13846.
29. Tanabe H, Qu X, Weeks CS, et al.: Structure-activity determinants in Paneth cell alpha-defensins: loss-of-function in mouse cryptdin-4 by charge-reversal at arginine residue positions. J Biol Chem 2004, 279:11976-11983. A careful, well-executed structure-function investigation.
30. Ganz T, Selsted ME, Szklarek D, et al.: Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 1985, 76:1427-1435.
31. Yang D, Chertov O, Oppenheim JJ: The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity. Cell Mol Life Sci 2001, 58:978-989.
32. Yang D, Biragyn A, Kwak LW, Oppenheim JJ: Mammalian defensins in immunity: more than just microbicidal. Trends Immunol 2002, 23:291-296.
33. Lencer WI, Cheung G, Strohmeier GR, et al.: Induction of epithelial chloride secretion by channel-forming cryptins 2 and 3. Proc Natl Acad Sci USA 1997, 94:8585-8589.
34. Yue G, Merlin D, Selsted ME, et al.: Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells. Am J Physiol Gastrointest Liver Physiol 2002, 282:G757-G765.
35. Lin PW, Simon PO, Gewirtz AT, et al.: Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response. J Biol Chem 2004, 279:19902-19907 [epub ahead of print]. A new activity suggests that some Paneth cell defensins may serve as paracrine signaling molecules.
36. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI: Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003, 4:269-273. An interesting new antimicrobial effector molecule of Paneth cells is identified.
37. Harder J, Schroder J: RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem 2002, 277:46779-46784.
38. Hornef MF, Pütsep K, Karlsson J, et al.: Increased variability of intestinal antimicrobial peptides by covalent dimer formation. Nat Immunol, in press. An abundant new family of antimicrobial peptides that are evolutionary related to α-defensins is characterized.
39. Huttner KM, Ouellette AJ: A family of defensin-like genes codes for diverse cysteine-rich peptides in mouse Paneth cells. Genomics 1994, 24:99-109.
40. Mallow EB, Harris A, Salzman N, et al.: Human enteric defensins: gene structure and developmental expression. J Biol Chem 1996, 271:4038-4045.
41. Ouellette AJ, Greco RM, James M, et al.: Developmental regulation of cryptdin, a corticostatin/defensin precursor mRNA in mouse small intestinal crypt epithelium. J Cell Biol 1989, 108:1687-1695.
42. Putsep K, Axelsson LG, Boman A, et al.: Germ-free and colonized mice generate the same products from enteric prodefensins. J Biol Chem 2000, 275:40478-40482.
43. Satoh Y, Habara Y, Ono K, Kanno T: Carbamylcholine- and catecholamine-induced intracellular calcium dynamics of epithelial cells in mouse ileal crypts. Gastroenterology 1995, 108:1345-1356.
44. Ayabe T, Wulff H, Darmoul D, et al.: Modulation of mouse Paneth cell alpha-defensin secretion by mlKCa1, a Ca2+-activated, intermediate conductance potassium channel. J Biol Chem 2002, 277:3793-3800.
45. Selsted ME, Miller SI, Henschen AH, Ouellette AJ: Enteric defensins: antibiotic peptide components of intestine host defense. J Cell Biol 1992, 118:929-936.
46. Shirafuji Y, Tanabe H, Satchell DP, et al.: Structural determinants of procryptdin recognition and cleavage by matrix metalloproteinase-7. J Biol Chem 2003, 278:7910-7919. Details of the processing of Paneth cell a-defensins in mice, and an interesting mouse strain variation are reported.
47. Porter EM, Poles MA, Lee JS, et al.: Isolation of human intestinal defensins from ileal neobladder urine. FEBS Lett 1998, 434:272-276.
48. Cunliffe RN, Rose FR, Keyte J, et al.: Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut 2001, 48:176-185.
49. Tanabe H, Yuan J, Zaragoza MM, et al.: Paneth cell alpha-defensins from rhesus macaque small intestine. Infect Immun 2004, 72:1470-1478. Primary structures of primate α-defensins provide interesting comparison with human orthologs.
50. Ayabe T, Satchell DP, Pesendorfer P, et al.: Activation of Paneth cell alpha -defensins in mouse small intestine. J Biol Chem 2002, 277:5219-5228.
51. Salzman NH, Chou MM, de Jong H, et al.: Enteric Salmonella infection inhibits Paneth cell antimicrobial peptide expression. Infect Immun 2003, 71:1109-1115. An interesting virulence mechanism is identified.
52. Gunn JS, Ryan SS, Van Velkinburgh JC, et al.: Genetic and functional analysis of a PmrA-PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar typhimurium. Infect Immun 2000, 68:6139-6146.
53. Ernst RK, Guina T, Miller SI: Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity. Microbes Infect 2001, 3:1327-1334.
54. Kamal M, Wakelin D, Ouellette AJ, et al.: Mucosal T cells regulate Paneth and intermediate cell numbers in the small intestine of T. spiralis-infected mice. Clin Exp Immunol 2001, 126:117-125.
55. Kamal M, Dehlawi MS, Brunet LR, Wakelin D: Paneth and intermediate cell hyperplasia induced in mice by helminth infections. Parasitology 2002, 125:275-281.
56. Sartor RB: Enteric microflora in IBD: pathogens or commensals? Inflamm Bowel Dis 1997, 3:230-235.
57. Hugot JP, Chamaillard M, Zouali H, et al.: Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001, 411:599-603.
58. Ogura Y, Bonen DK, Inohara N, et al.: A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001, 411:603-606.
59. Ogura Y, Lala S, Xin W, et al.: Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis. Gut 2003, 52:1591-1597. Expression of NOD2 in Paneth cells provides an interesting new clue to possible mechanism of disease pathogenesis in Crohn disease.
60. Lala S, Ogura Y, Osborne C, et al.: Crohn's disease and the NOD2 gene: a role for Paneth cells. Gastroenterology 2003, 125:47-57. Expression of NOD2 in Paneth cells provides an interesting new clue to possible mechanism of disease pathogenesis in Crohn disease.
61. Aldhous MC, Nimmo ER, Satsangi J: NOD2/CARD15 and the Paneth cell: another piece in the genetic jigsaw of inflammatory bowel disease. Gut 2003, 52:1533-1535.
62. Fellermann K, Wehkamp J, Herrlinger KR, Stange EF: Crohn's disease: a defensin deficiency syndrome? Eur J Gastroenterol Hepatol 2003, 15:627-634. A provocative question that appears to have some interesting answers.
63. Wehkamp J, Harder J, Weichenthal M, et al.: NOD2 (CARD15) mutations in Crohns disease are associated with diminished mucosal alpha-defensin expression. Gut, in press. These exciting data support a clear link of Paneth cell defensins and Crohn disease.
64. Sartor RB: Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology 2004, 126:1620-1633.
65. Cuthbert AP, Fisher SA, Mirza MM, et al.: The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology 2002, 122:867-874.
66. Brown EG, Sweet AY: Neonatal necrotizing enterocolitis. Pediatr Clin North Am 1982, 29:1149-1170.
67. Salzman NH, Polin RA, Harris MC, et al.: Enteric defensin expression in necrotizing enterocolitis. Pediatr Res 1998, 44:20-26.
68. Coutinho HB, da Mota HC, Coutinho VB, et al.: Absence of lysozyme (muramidase) in the intestinal Paneth cells of newborn infants with necrotising enterocolitis. J Clin Pathol 1998, 51:512-514.
69. Clarke LL, Gawenis LR, Bradford EM, et al.: Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice. Am J Physiol Gastrointest Liver Physiol 2004, 286:G1050-G1058. Dramatic observations may spawn new studies on pathophysiology of intestinal manifestations of cystic fibrosis.
70. Trezise AE, Romano PR, Gill DR, et al.: The multidrug resistance and cystic fibrosis genes have complementary patterns of epithelial expression. EMBO J 1992, 11:4291-4303.
71. Kelly P, Feakins R, Domizio P, et al.: Paneth cell granule depletion in the human small intestine under infective and nutritional stress. Clin Exp Immunol 2004, 135:303-309. An interesting study that examines biopsies from a tropical population.
72. Wilson ID, McClain CJ, Erlandsen SL: Ileal Paneth cells and IgA system in rats with severe zinc deficiency: an immunohistochemical and morphological study. Histochem J 1980, 12:457-471.
73. Sherman MP, Bennett S, Hwang F, Sherman J: Innate immunity and bacterial infection in the neonatal small intestine: Importance of Paneth cell integrity. Pediatr Res 2004, 55:391A.
74. Sancho E, Batlle E, Clevers H: Live and let die in the intestinal epithelium. Curr Opin Cell Biol 2003, 15:763-770. Excellent review on fascinating details of cell lineage differentiation.
75. de Santa Barbara P, van den Brink GR, Roberts DJ: Development and differentiation of the intestinal epithelium. Cell Mol Life Sci 2003, 60:1322-1332.
76. Yang Q, Bermingham NA, Finegold MJ, Zoghbi HY: Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science 2001, 294:2155-2158.
77. Stappenbeck TS, Mills JC, Gordon JI: Molecular features of adult mouse small intestinal epithelial progenitors. Proc Natl Acad Sci USA 2003, 100:1004-1009.
78. Blache P, Van De Wetering M, Duluc I, et al.: SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes. J Cell Biol 2004, 166:37-47.
79. Batlle E, Henderson JT, Beghtel H, et al.: Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 2002, 111:251-263.
80. Stappenbeck TS, Gordon JI: Rac1 mutations produce aberrant epithelial differentiation in the developing and adult mouse small intestine. Development 2000, 127:2629-2642.
81. Husoy T, Hb OL, Knutsen HK, et al.: Truncated mouse adenomatous polyposis coli reduces connexin32 content and increases matrilysin secretion from Paneth cells. Eur J Cancer 2004, 40:1599-1603.
82. Stappenbeck TS, Hooper LV, Gordon JI: Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 2002, 99:15451-15455.