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PMID: 22728527 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Epithelial antimicrobial defence of the skin and intestine.

Nature reviews. Immunology ·Vol. 12 ·No. 7 ·2012-06-25 ·Pages 503-16

Gallo RL, Hooper LV

Abstract

Surface tissues of the body such as the skin and intestinal tract are in direct contact with the external environment and are thus continuously exposed to large numbers of microorganisms. To cope with the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins that directly kill or inhibit the growth of microorganisms. In this Review, we highlight new advances in our understanding of how epithelial antimicrobial proteins protect against pathogens and contribute to microbiota-host homeostasis at the skin and gut mucosae. Further, we discuss recent insights into the regulatory mechanisms that control antimicrobial protein expression. Finally, we consider how impaired antimicrobial protein expression and function can contribute to disease.

MeSH Terms
Animals Antimicrobial Cationic Peptides/immunology Epithelium/immunology,microbiology Host-Pathogen Interactions/immunology Humans Intestinal Mucosa/immunology,microbiology Metagenome/immunology Mice Models, Immunological Skin/immunology,microbiology
Chemicals
Antimicrobial Cationic Peptides
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gallo Richard L
Division of Dermatology, Department of Medicine, University of California-San Diego, San Diego, California 92093, USA. rgallo@ucsd.edu
Hooper Lora V
References (139)
139 references, click to expand
  1. Dermcidin: a novel human antibiotic peptide secreted by sweat glands.
    Nat Immunol. 2001 Dec;2(12):1133-7 PMID: 11694882
  2. Severity of Staphylococcus aureus infection of the skin is associated with inducibility of human beta-defensin 3 but not human beta-defensin 2.
    Infect Immun. 2010 Jul;78(7):3112-7 PMID: 20404083
  3. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides.
    J Biol Chem. 1999 Mar 26;274(13):8405-10 PMID: 10085071
  4. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits.
    Nature. 2008 Oct 9;455(7214):804-7 PMID: 18724361
  5. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense.
    Trends Immunol. 2009 Mar;30(3):131-41 PMID: 19217824
  6. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide.
    Nature. 2007 Oct 4;449(7162):564-9 PMID: 17873860
  7. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine.
    Cell Host Microbe. 2009 May 8;5(5):476-86 PMID: 19454351
  8. Genetic variants of Wnt transcription factor TCF-4 (TCF7L2) putative promoter region are associated with small intestinal Crohn's disease.
    PLoS One. 2009;4(2):e4496 PMID: 19221600
  9. Regulation of C-type lectin antimicrobial activity by a flexible N-terminal prosegment.
    J Biol Chem. 2009 Feb 20;284(8):4881-8 PMID: 19095652
  10. Cathelicidins--a family of multifunctional antimicrobial peptides.
    Cell Mol Life Sci. 2003 Apr;60(4):711-20 PMID: 12785718
  11. Nod2 is required for the regulation of commensal microbiota in the intestine.
    Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15813-8 PMID: 19805227
  12. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.
    Nature. 2008 Nov 13;456(7219):259-63 PMID: 18849966
  13. Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human beta-defensin-3.
    J Allergy Clin Immunol. 2008 Jul;122(1):62-8 PMID: 18538383
  14. Mammalian antimicrobial peptide influences control of cutaneous Leishmania infection.
    Cell Microbiol. 2011 Jun;13(6):913-23 PMID: 21501359
  15. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis.
    Immunology. 2002 May;106(1):20-6 PMID: 11972628
  16. Structural, functional analysis and localization of the human CAP18 gene.
    FEBS Lett. 1996 Nov 25;398(1):74-80 PMID: 8946956
  17. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin.
    Nature. 2003 Apr 3;422(6931):522-6 PMID: 12660734
  18. Evolution of mammals and their gut microbes.
    Science. 2008 Jun 20;320(5883):1647-51 PMID: 18497261
  19. Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice.
    J Biol Chem. 1997 Sep 19;272(38):23729-40 PMID: 9295317
  20. Bacterial resistance mechanisms against host defense peptides.
    Cell Mol Life Sci. 2011 Jul;68(13):2243-54 PMID: 21560069
  21. Control of epithelial cell function by interleukin-22-producing RORγt+ innate lymphoid cells.
    Immunology. 2011 Apr;132(4):453-65 PMID: 21391996
  22. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family.
    Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1829-33 PMID: 9465102
  23. 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 Nov;68(11):6139-46 PMID: 11035717
  24. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.
    Nat Med. 2006 Jun;12(6):636-41 PMID: 16751768
  25. A peptide antibiotic from human skin.
    Nature. 1997 Jun 26;387(6636):861 PMID: 9202117
  26. Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse.
    J Biol Chem. 1997 May 16;272(20):13088-93 PMID: 9148921
  27. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease.
    Nature. 2001 May 31;411(6837):603-6 PMID: 11385577
  28. The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine.
    Science. 2011 Oct 14;334(6053):255-8 PMID: 21998396
  29. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus.
    Immunity. 2006 Mar;24(3):341-8 PMID: 16546102
  30. Mammalian defensins in immunity: more than just microbicidal.
    Trends Immunol. 2002 Jun;23(6):291-6 PMID: 12072367
  31. Secreted enteric antimicrobial activity localises to the mucus surface layer.
    Gut. 2008 Jun;57(6):764-71 PMID: 18250125
  32. Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds.
    Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11035-9 PMID: 7972004
  33. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea.
    Nat Med. 2007 Aug;13(8):975-80 PMID: 17676051
  34. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria.
    Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15064-9 PMID: 18806221
  35. Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement.
    J Invest Dermatol. 2008 Dec;128(12):2880-7 PMID: 18580964
  36. Germ-free and colonized mice generate the same products from enteric prodefensins.
    J Biol Chem. 2000 Dec 22;275(51):40478-82 PMID: 11010975
  37. Reduced Paneth cell alpha-defensins in ileal Crohn's disease.
    Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18129-34 PMID: 16330776
  38. Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant.
    J Immunol. 2005 May 15;174(10):6257-65 PMID: 15879124
  39. Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways.
    Gut. 2003 May;52(5):735-41 PMID: 12692061
  40. HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells.
    Am J Physiol. 1996 Dec;271(6 Pt 1):G993-1002 PMID: 8997243
  41. Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor.
    J Clin Invest. 2006 Jul;116(7):1878-85 PMID: 16778986
  42. [beta]-defensins in lung host defense.
    Annu Rev Physiol. 2002;64:709-48 PMID: 11826286
  43. Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus.
    Cell Host Microbe. 2011 Aug 18;10(2):158-64 PMID: 21843872
  44. Cathelicidin antimicrobial peptides block dendritic cell TLR4 activation and allergic contact sensitization.
    J Immunol. 2007 Feb 1;178(3):1829-34 PMID: 17237433
  45. Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1.
    Nature. 2011 Jan 20;469(7330):419-23 PMID: 21248850
  46. The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders.
    J Biol Chem. 1997 Jun 13;272(24):15258-63 PMID: 9182550
  47. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense.
    Science. 1999 Oct 1;286(5437):113-7 PMID: 10506557
  48. Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes.
    Proc Natl Acad Sci U S A. 1990 Jan;87(1):210-4 PMID: 1688654
  49. Unravelling the pathogenesis of inflammatory bowel disease.
    Nature. 2007 Jul 26;448(7152):427-34 PMID: 17653185
  50. Pro-rich antimicrobial peptides from animals: structure, biological functions and mechanism of action.
    Curr Pharm Des. 2002;8(9):763-78 PMID: 11945170
  51. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37.
    J Immunol. 2005 Oct 1;175(7):4662-8 PMID: 16177113
  52. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.
    Nature. 2001 May 31;411(6837):599-603 PMID: 11385576
  53. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6.
    Science. 1999 Oct 15;286(5439):525-8 PMID: 10521347
  54. Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors.
    J Immunol. 2003 Jun 1;170(11):5583-9 PMID: 12759437
  55. Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus.
    J Invest Dermatol. 2001 Jul;117(1):91-7 PMID: 11442754
  56. High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis.
    J Invest Dermatol. 2005 Dec;125(6):1163-73 PMID: 16354186
  57. Molecular basis for peptidoglycan recognition by a bactericidal lectin.
    Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7722-7 PMID: 20382864
  58. Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers.
    J Invest Dermatol. 2008 Apr;128(4):917-25 PMID: 17943185
  59. Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37).
    J Leukoc Biol. 2001 May;69(5):691-7 PMID: 11358975
  60. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin.
    J Biol Chem. 2002 Nov 29;277(48):46779-84 PMID: 12244054
  61. The gut microflora and intestinal epithelial cells: a continuing dialogue.
    Microbes Infect. 2002 Mar;4(3):309-17 PMID: 11909741
  62. Bactericidal properties of murine intestinal phospholipase A2.
    J Clin Invest. 1995 Feb;95(2):603-10 PMID: 7860744
  63. Molecular analysis of commensal host-microbial relationships in the intestine.
    Science. 2001 Feb 2;291(5505):881-4 PMID: 11157169
  64. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes.
    J Invest Dermatol. 2011 Mar;131(3):688-97 PMID: 21107351
  65. Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide.
    J Immunol. 2003 Mar 1;170(5):2274-8 PMID: 12594247
  66. History of eczema herpeticum is associated with the inability to induce human β-defensin (HBD)-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis.
    Br J Dermatol. 2010 Sep;163(3):659-61 PMID: 20545685
  67. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism.
    J Clin Invest. 2007 Mar;117(3):803-11 PMID: 17290304
  68. Cathelicidin-deficient (Cnlp -/- ) mice show increased susceptibility to Pseudomonas aeruginosa keratitis.
    Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4498-508 PMID: 17898271
  69. Immunohistological pointers to a possible role for excessive cathelicidin (LL-37) expression by apocrine sweat glands in the pathogenesis of hidradenitis suppurativa/acne inversa.
    Br J Dermatol. 2012 May;166(5):1023-34 PMID: 22136668
  70. Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci.
    Infect Immun. 2010 Jun;78(6):2793-800 PMID: 20385753
  71. Innate immune lectins kill bacteria expressing blood group antigen.
    Nat Med. 2010 Mar;16(3):295-301 PMID: 20154696
  72. Administration of oral vitamin D induces cathelicidin production in atopic individuals.
    J Allergy Clin Immunol. 2008 Oct;122(4):829-831 PMID: 19014773
  73. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.
    Eur J Biochem. 1996 Jun 1;238(2):325-32 PMID: 8681941
  74. Association of a functional variant in the Wnt co-receptor LRP6 with early onset ileal Crohn's disease.
    PLoS Genet. 2012;8(2):e1002523 PMID: 22393312
  75. Insect immunity: isolation from immune blood of the dipteran Phormia terranovae of two insect antibacterial peptides with sequence homology to rabbit lung macrophage bactericidal peptides.
    Proc Natl Acad Sci U S A. 1989 Jan;86(1):262-6 PMID: 2911573
  76. The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6.
    Infect Immun. 1999 May;67(5):2561-6 PMID: 10225921
  77. Innate defenses of the intestinal epithelial barrier.
    Cell Mol Life Sci. 2005 Jun;62(12):1297-307 PMID: 15971105
  78. Peptidoglycan recognition proteins: modulators of the microbiome and inflammation.
    Nat Rev Immunol. 2011 Nov 11;11(12):837-51 PMID: 22076558
  79. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression.
    J Immunol. 2004 Sep 1;173(5):2909-12 PMID: 15322146
  80. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells.
    J Exp Med. 2000 Oct 2;192(7):1069-74 PMID: 11015447
  81. Developmental switch of intestinal antimicrobial peptide expression.
    J Exp Med. 2008 Jan 21;205(1):183-93 PMID: 18180308
  82. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.
    FASEB J. 2005 Jul;19(9):1067-77 PMID: 15985530
  83. Flagellin is the principal inducer of the antimicrobial peptide S100A7c (psoriasin) in human epidermal keratinocytes exposed to Escherichia coli.
    FASEB J. 2008 Jul;22(7):2168-76 PMID: 18263703
  84. Secretory phospholipase A2 is the principal bactericide for staphylococci and other gram-positive bacteria in human tears.
    Infect Immun. 1998 Jun;66(6):2791-7 PMID: 9596749
  85. BsmI polymorphism of the vitamin D receptor gene in patients with the fulminant course of rosacea conglobata (rosacea fulminans).
    J Dermatol. 2004 Mar;31(3):244-6 PMID: 15187348
  86. IL-22 increases the innate immunity of tissues.
    Immunity. 2004 Aug;21(2):241-54 PMID: 15308104
  87. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection.
    J Biol Chem. 2003 Mar 14;278(11):8869-72 PMID: 12527755
  88. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
    Cell. 2008 Sep 5;134(5):743-56 PMID: 18775308
  89. Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides.
    J Immunol. 2012 Jan 1;188(1):345-57 PMID: 22140255
  90. The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils.
    Blood. 1997 Oct 1;90(7):2796-803 PMID: 9326247
  91. Increased expression of HIP/PAP and regenerating gene III in human inflammatory bowel disease and a murine bacterial reconstitution model.
    Inflamm Bowel Dis. 2003 May;9(3):162-70 PMID: 12792221
  92. Constitutive expression of the antimicrobial peptide RNase 7 is associated with Staphylococcus aureus infection of the skin.
    J Infect Dis. 2009 Dec 15;200(12):1907-15 PMID: 19919305
  93. Identification of Legionella pneumophila rcp, a pagP-like gene that confers resistance to cationic antimicrobial peptides and promotes intracellular infection.
    Infect Immun. 2001 Jul;69(7):4276-86 PMID: 11401964
  94. Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology.
    Microbiol Mol Biol Rev. 1998 Dec;62(4):1157-70 PMID: 9841668
  95. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator.
    Nat Med. 2001 Feb;7(2):180-5 PMID: 11175848
  96. Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium.
    Infect Immun. 2002 Feb;70(2):953-63 PMID: 11796631
  97. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88.
    Science. 2007 Jul 6;317(5834):124-7 PMID: 17615359
  98. alpha2-Macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobial peptide LL-37.
    J Biol Chem. 2004 Dec 17;279(51):52820-3 PMID: 15520011
  99. Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin.
    J Invest Dermatol. 2002 Nov;119(5):1090-5 PMID: 12445197
  100. Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis.
    Gut. 2003 Nov;52(11):1591-7 PMID: 14570728
  101. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization.
    Nature. 2010 May 20;465(7296):346-9 PMID: 20485435
  102. Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets.
    J Allergy Clin Immunol. 2007 Jul;120(1):13-22 PMID: 17606031
  103. MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection.
    J Exp Med. 2007 Aug 6;204(8):1891-900 PMID: 17635956
  104. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface.
    Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20858-63 PMID: 19075245
  105. Paneth cell trypsin is the processing enzyme for human defensin-5.
    Nat Immunol. 2002 Jun;3(6):583-90 PMID: 12021776
  106. The skin microbiome.
    Nat Rev Microbiol. 2011 Apr;9(4):244-53 PMID: 21407241
  107. Bacterial community variation in human body habitats across space and time.
    Science. 2009 Dec 18;326(5960):1694-7 PMID: 19892944
  108. Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection.
    Nat Immunol. 2005 Jan;6(1):57-64 PMID: 15568027
  109. Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection.
    J Infect Dis. 2010 Feb 15;201(4):534-43 PMID: 20064069
  110. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases.
    Antimicrob Agents Chemother. 2004 Dec;48(12):4673-9 PMID: 15561843
  111. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.
    Nature. 2004 Dec 16;432(7019):917-21 PMID: 15531878
  112. Endogenous antimicrobial peptides and skin infections in atopic dermatitis.
    N Engl J Med. 2002 Oct 10;347(15):1151-60 PMID: 12374875
  113. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
    Science. 2006 Mar 24;311(5768):1770-3 PMID: 16497887
  114. Developmental microbial ecology of the neonatal gastrointestinal tract.
    Am J Clin Nutr. 1999 May;69(5):1035S-1045S PMID: 10232646
  115. Innate antimicrobial peptide protects the skin from invasive bacterial infection.
    Nature. 2001 Nov 22;414(6862):454-7 PMID: 11719807
  116. Induction of beta-defensin 3 in keratinocytes stimulated by bacterial lipopeptides through toll-like receptor 2.
    Microbes Infect. 2006 May;8(6):1513-21 PMID: 16697678
  117. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease.
    J Clin Microbiol. 2005 Jul;43(7):3380-9 PMID: 16000463
  118. Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin.
    J Invest Dermatol. 2010 Jan;130(1):192-200 PMID: 19710683
  119. Antimicrobial peptides of multicellular organisms.
    Nature. 2002 Jan 24;415(6870):389-95 PMID: 11807545
  120. Inhibition of virulence factor expression in Staphylococcus aureus by the Staphylococcus epidermidis agr pheromone and derivatives.
    FEBS Lett. 1999 May 7;450(3):257-62 PMID: 10359085
  121. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract.
    Science. 2005 Feb 4;307(5710):731-4 PMID: 15692051
  122. In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes.
    Blood. 1986 Dec;68(6):1407-10 PMID: 3779104
  123. Metal chelation and inhibition of bacterial growth in tissue abscesses.
    Science. 2008 Feb 15;319(5865):962-5 PMID: 18276893
  124. Symbiotic bacteria direct expression of an intestinal bactericidal lectin.
    Science. 2006 Aug 25;313(5790):1126-30 PMID: 16931762
  125. Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin.
    FASEB J. 2006 Oct;20(12):2068-80 PMID: 17012259
  126. Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor.
    Proc Natl Acad Sci U S A. 1987 Aug;84(15):5449-53 PMID: 3299384
  127. Paneth cell α-defensins in enteric innate immunity.
    Cell Mol Life Sci. 2011 Jul;68(13):2215-29 PMID: 21560070
  128. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells.
    Nat Immunol. 2009 Jan;10(1):83-91 PMID: 19029903
  129. Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium.
    J Immunol. 1999 Dec 15;163(12):6718-24 PMID: 10586069
  130. Diversity of the human intestinal microbial flora.
    Science. 2005 Jun 10;308(5728):1635-8 PMID: 15831718
  131. Enteric defensins are essential regulators of intestinal microbial ecology.
    Nat Immunol. 2010 Jan;11(1):76-83 PMID: 19855381
  132. Wnt signalling induces maturation of Paneth cells in intestinal crypts.
    Nat Cell Biol. 2005 Apr;7(4):381-6 PMID: 15778706
  133. Induction of intestinal Th17 cells by segmented filamentous bacteria.
    Cell. 2009 Oct 30;139(3):485-98 PMID: 19836068
  134. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria.
    Nat Immunol. 2000 Aug;1(2):113-8 PMID: 11248802
  135. Role of charge properties of bacterial envelope in bactericidal action of human group IIA phospholipase A2 against Staphylococcus aureus.
    J Biol Chem. 2002 Dec 6;277(49):47636-44 PMID: 12359734
  136. Multi-layered regulation of intestinal antimicrobial defense.
    Cell Mol Life Sci. 2008 Oct;65(19):3019-27 PMID: 18560756
  137. Angiogenins: a new class of microbicidal proteins involved in innate immunity.
    Nat Immunol. 2003 Mar;4(3):269-73 PMID: 12548285
  138. Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum.
    J Immunol. 2004 Feb 1;172(3):1763-7 PMID: 14734759
  139. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens.
    J Immunol. 2005 Apr 15;174(8):4901-7 PMID: 15814717
Article Info
Journal
Nature reviews. Immunology
Abbr.
Nat Rev Immunol
ISSN
1474-1741
DOI
10.1038/nri3228
Email
rgallo@ucsd.edu
Published
2012-06-25
Epub
2012-00-25
Pages
503-16
Language
English
Region
England
NLM ID
101124169
PMCID
PMC3563335
Subset
IM
Grants
NIAID NIH HHS · R37 AI052453 · United States
NIDDK NIH HHS · R01 DK070855 · United States
NIAID NIH HHS · R56 AI083358 · United States
NIAID NIH HHS · AI083358 · United States
Howard Hughes Medical Institute · United States
NIAID NIH HHS · HHSN272201000020I · United States
NIAMS NIH HHS · R01 AR052728 · United States
NIAID NIH HHS · HHSN272201000020C · United States
NIAID NIH HHS · R01 AI052453 · United States
NIAID NIH HHS · R01 AI083358 · United States
NIAID NIH HHS · AI052453 · United States
NIDDK NIH HHS · DK070855 · United States
NIAMS NIH HHS · AR052728 · United States
External Links
PubMed source DOI: 10.1038/nri3228 PMC Full Text View journal details
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