title: Toll-like receptors in skin infections and inflammatory diseases.
abstract: The skin is the ultimate example of the function of innate immunity, it alerts the host of danger by many systems including sensing pathogen-associated molecule patterns (PAMPs) through Toll-like receptors and other pattern recognition receptors (PRRs), yet normally provides defense without inflammation. The skin responds rapidly to invading microbes by producing antimicrobial peptides or other antimicrobial intermediates before cytokine release results in inflammation. To achieve maximal immune responses for clearing invading microbes, the activation of select PRRs in skin then initiates and shapes adaptive immune responses through the activation of dendritic cells and recruitment of T cell subsets. Importantly, cross-talk between TLRs can influence this system in several ways including augmenting or suppressing the immune response. As a consequence of their pivotal role, TLR responses need to be tightly controlled by associated negative regulators or negative feedback loops to prevent detrimental effects from TLRs overactivation. This review focuses on describing the involvement of TLRs in the development of skin infections and inflammatory diseases, and highlights the potential application of TLR agonists or antagonists in these skin diseases.
authors.affiliation: Division of Dermatology, University of California, San Diego, Dermatology Section, VA San Diego Healthcare System, San Diego, California 92161, USA.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Lai
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003872:Dermatitis / Q000188:drug therapy / Q000276:immunology*; D025461:Feedback, Physiological; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology*; D012874:Skin Diseases, Infectious / Q000188:drug therapy / Q000276:immunology*; D051193:Toll-Like Receptors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D051193:Toll-Like Receptors
references.citation: Science. 1998 Dec 11;282(5396):2085-8
references.pmid: 9851930
references.citation: Nat Rev Immunol. 2003 Feb;3(2):169-76
references.pmid: 12563300
references.citation: J Biol Chem. 2003 Oct 24;278(43):41702-8
references.pmid: 12871942
references.citation: J Biol Chem. 2003 Jul 4;278(27):24526-32
references.pmid: 12721283
references.citation: Science. 2004 Mar 5;303(5663):1522-6
references.pmid: 15001781
references.citation: J Clin Invest. 2004 May;113(10):1473-81
references.pmid: 15146245
references.citation: Nat Immunol. 2006 Feb;7(2):139-47
references.pmid: 16378096
references.citation: World J Gastroenterol. 2006 Apr 14;12(14):2149-60
references.pmid: 16610014
references.citation: Nature. 2007 Jun 21;447(7147):972-8
references.pmid: 17538624
references.citation: Nat Immunol. 2004 Oct;5(10):1052-60
references.pmid: 15334086
references.citation: Nature. 2007 Oct 4;449(7162):564-9
references.pmid: 17873860
references.citation: J Immunol. 2003 Sep 15;171(6):3154-62
references.pmid: 12960343
references.citation: Arch Pathol Lab Med. 2003 Feb;127(2):178-86
references.pmid: 12562231
references.citation: Annu Rev Immunol. 2004;22:181-215
references.pmid: 15032578
references.citation: Nat Immunol. 2004 May;5(5):503-7
references.pmid: 15064760
references.citation: Science. 2003 Aug 1;301(5633):640-3
references.pmid: 12855817
references.citation: Blood. 2006 Jan 15;107(2):610-8
references.pmid: 16174756
references.citation: J Infect Dis. 1998 Aug;178(2):551-5
references.pmid: 9697742
references.citation: J Biol Chem. 2004 Apr 23;279(17):17079-84
references.pmid: 14764599
references.citation: Nature. 1996 Oct 3;383(6599):443-6
references.pmid: 8837778
references.citation: Clin Microbiol Rev. 2008 Jan;21(1):13-25
references.pmid: 18202435
references.citation: J Invest Dermatol. 1998 May;110(5):734-9
references.pmid: 9579537
references.citation: Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8222-6
references.pmid: 9653168
references.citation: J Rheumatol. 2002 Jun;29(6):1176-82
references.pmid: 12064831
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: J Immunol. 2004 Sep 1;173(5):2913-7
references.pmid: 15322147
references.citation: Science. 1997 Oct 31;278(5339):866-9
references.pmid: 9346485
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15416-21
references.pmid: 15492225
references.citation: Annu Rev Immunol. 2003;21:335-76
references.pmid: 12524386
references.citation: J Biol Chem. 2001 Oct 5;276(40):37692-9
references.pmid: 11477091
references.citation: Nat Rev Immunol. 2001 Nov;1(2):135-45
references.pmid: 11905821
references.citation: Biochem Biophys Res Commun. 2002 Nov 29;299(2):216-21
references.pmid: 12437972
references.citation: Int J Lepr. 1965 Jul-Sep;33(3):Suppl:533-41
references.pmid: 5892587
references.citation: Nat Immunol. 2001 Aug;2(8):675-80
references.pmid: 11477402
references.citation: Semin Immunol. 2007 Feb;19(1):41-7
references.pmid: 17280841
references.citation: J Exp Med. 1998 Sep 7;188(5):985-90
references.pmid: 9730900
references.citation: Curr Pharm Des. 2006;12(32):4215-28
references.pmid: 17100624
references.citation: Curr Pharm Des. 2006;12(32):4123-34
references.pmid: 17100615
references.citation: Immunol Rev. 2004 Dec;202:8-32
references.pmid: 15546383
references.citation: Clin Exp Allergy. 2006 Aug;36(8):1049-62
references.pmid: 16911361
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3533-8
references.pmid: 14982987
references.citation: Mol Cell Biol. 2002 Oct;22(20):7158-67
references.pmid: 12242293
references.citation: J Invest Dermatol. 2008 Apr;128(4):816-24
references.pmid: 17943182
references.citation: Immunity. 2006 Jan;24(1):79-91
references.pmid: 16413925
references.citation: Nat Immunol. 2005 Aug;6(8):769-76
references.pmid: 15995707
references.citation: J Interferon Cytokine Res. 2003 Jan;23(1):13-23
references.pmid: 12639295
references.citation: J Infect Dis. 2005 Mar 1;191(5):746-8
references.pmid: 15688290
references.citation: J Neurochem. 2005 Jul;94(2):289-98
references.pmid: 15998280
references.citation: Br J Dermatol. 2003 Apr;148(4):670-9
references.pmid: 12752123
references.citation: J Immunol. 2000 Nov 15;165(10):5392-6
references.pmid: 11067888
references.citation: J Biol Chem. 2003 Dec 12;278(50):49751-62
references.pmid: 14519765
references.citation: Arch Dermatol Res. 2006 Jan;297(7):280-8
references.pmid: 16283346
references.citation: Eur J Immunol. 2004 Mar;34(3):796-805
references.pmid: 14991609
references.citation: J Immunol. 2007 Feb 1;178(3):1829-34
references.pmid: 17237433
references.citation: J Exp Med. 2003 Oct 6;198(7):1043-55
references.pmid: 14517278
references.citation: Br J Dermatol. 2005 Dec;153(6):1105-13
references.pmid: 16307644
references.citation: Eur J Immunol. 2006 Jan;36(1):199-206
references.pmid: 16323247
references.citation: J Clin Invest. 1985 Oct;76(4):1427-35
references.pmid: 2997278
references.citation: Nature. 2001 Oct 18;413(6857):732-8
references.pmid: 11607032
references.citation: Immunol Rev. 2000 Apr;174:192-209
references.pmid: 10807517
references.citation: Nat Immunol. 2004 Oct;5(10):987-95
references.pmid: 15454922
references.citation: J Leukoc Biol. 2001 May;69(5):691-7
references.pmid: 11358975
references.citation: Nature. 2001 Sep 6;413(6851):78-83
references.pmid: 11544529
references.citation: Clin Exp Immunol. 2006 Apr;144(1):1-9
references.pmid: 16542358
references.citation: Eur J Immunol. 2001 Nov;31(11):3131-7
references.pmid: 11745329
references.citation: N Engl J Med. 1998 Aug 20;339(8):520-32
references.pmid: 9709046
references.citation: J Virol. 2005 Mar;79(5):2910-9
references.pmid: 15709010
references.citation: Nat Immunol. 2001 Sep;2(9):835-41
references.pmid: 11526399
references.citation: Science. 1999 Oct 15;286(5439):420-1
references.pmid: 10577203
references.citation: J Immunol. 1999 Sep 1;163(5):2821-8
references.pmid: 10453027
references.citation: J Immunol. 2002 Dec 15;169(12):6668-72
references.pmid: 12471095
references.citation: Cell. 1997 Jul 25;90(2):373-83
references.pmid: 9244310
references.citation: Science. 1997 Oct 31;278(5339):860-6
references.pmid: 9346484
references.citation: Science. 2004 May 14;304(5673):1014-8
references.pmid: 15143282
references.citation: J Exp Med. 1998 Feb 16;187(4):461-8
references.pmid: 9463396
references.citation: J Leukoc Biol. 2000 Apr;67(4):508-14
references.pmid: 10770283
references.citation: J Immunol. 2002 Aug 1;169(3):1535-41
references.pmid: 12133981
references.citation: Curr Opin Immunol. 2002 Feb;14(1):103-10
references.pmid: 11790539
references.citation: J Exp Med. 2000 Oct 2;192(7):1069-74
references.pmid: 11015447
references.citation: J Invest Dermatol. 2007 Feb;127(2):331-41
references.pmid: 17068485
references.citation: J Immunol. 2001 Nov 15;167(10):5887-94
references.pmid: 11698465
references.citation: Nat Immunol. 2004 Feb;5(2):190-8
references.pmid: 14716310
references.citation: Trends Immunol. 2003 Jun;24(6):286-90
references.pmid: 12810098
references.citation: FASEB J. 2008 Jul;22(7):2168-76
references.pmid: 18263703
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Nat Immunol. 2004 Oct;5(10):975-9
references.pmid: 15454920
references.citation: Nat Immunol. 2001 Oct;2(10):947-50
references.pmid: 11547333
references.citation: J Immunol. 2004 Apr 15;172(8):4987-94
references.pmid: 15067080
references.citation: J Biol Chem. 2003 Mar 14;278(11):8869-72
references.pmid: 12527755
references.citation: Nat Rev Immunol. 2004 Jul;4(7):512-20
references.pmid: 15229470
references.citation: J Immunol. 2000 Dec 1;165(11):6308-13
references.pmid: 11086067
references.citation: J Exp Med. 2004 Jun 21;199(12):1631-40
references.pmid: 15197227
references.citation: Am J Respir Cell Mol Biol. 2004 Oct;31(4):463-9
references.pmid: 15242847
references.citation: J Immunol. 2004 Jul 15;173(2):1179-83
references.pmid: 15240708
references.citation: Cell. 1996 Sep 20;86(6):973-83
references.pmid: 8808632
references.citation: J Mol Med (Berl). 2002 Sep;80(9):549-61
references.pmid: 12226737
references.citation: J Immunol. 2003 Oct 15;171(8):4304-10
references.pmid: 14530355
references.citation: Arthritis Rheum. 2004 May;50(5):1686-9
references.pmid: 15146440
references.citation: Curr Opin Immunol. 2006 Feb;18(1):24-30
references.pmid: 16337365
references.citation: Curr Pharm Des. 2006;12(32):4135-42
references.pmid: 17100616
references.citation: Nat Immunol. 2003 Feb;4(2):161-7
references.pmid: 12539043
references.citation: J Am Acad Dermatol. 2006 Jun;54(6):951-83; quiz 983-6
references.pmid: 16713451
references.citation: Nat Med. 1999 Jun;5(6):702-5
references.pmid: 10371511
references.citation: J Biol Chem. 2007 Jun 22;282(25):18265-18275
references.pmid: 17400552
references.citation: Int Immunol. 2006 Jul;18(7):1115-26
references.pmid: 16728430
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13831-6
references.pmid: 16954184
references.citation: Cell. 1997 Oct 17;91(2):243-52
references.pmid: 9346241
references.citation: Int Immunol. 2005 Jan;17(1):1-14
references.pmid: 15585605
references.citation: Semin Cutan Med Surg. 2005 Jun;24(2):73-8
references.pmid: 16092794
references.citation: J Immunol. 2007 Nov 15;179(10):7110-20
references.pmid: 17982103
references.citation: Drug Discov Today. 2007 Jan;12(1-2):80-7
references.pmid: 17198976
references.citation: Annu Rev Immunol. 2000;18:621-63
references.pmid: 10837071
references.citation: Int Immunol. 2006 Feb;18(2):355-62
references.pmid: 16373361
references.citation: Nature. 2002 Apr 18;416(6882):750-6
references.pmid: 11923871
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18631-5
references.pmid: 18006661
references.citation: Immunity. 1999 Oct;11(4):443-51
references.pmid: 10549626
references.citation: Nature. 1997 Jul 24;388(6640):394-7
references.pmid: 9237759
references.citation: Annu Rev Immunol. 2000;18:767-811
references.pmid: 10837075
references.citation: N Engl J Med. 2002 Oct 10;347(15):1151-60
references.pmid: 12374875
references.citation: Science. 2006 Mar 24;311(5768):1770-3
references.pmid: 16497887
references.citation: J Biol Chem. 2001 Nov 9;276(45):41661-7
references.pmid: 11518704
references.citation: Immunology. 2005 Apr;114(4):531-41
references.pmid: 15804290
references.citation: Nature. 2002 Jan 24;415(6870):389-95
references.pmid: 11807545
references.citation: Microbes Infect. 2006 May;8(6):1513-21
references.pmid: 16697678
references.citation: J Biol Chem. 2003 May 9;278(19):16713-9
references.pmid: 12609980
references.citation: Nature. 2003 Nov 6;426(6962):33-8
references.pmid: 14603309
references.citation: Infect Immun. 2001 Mar;69(3):1477-82
references.pmid: 11179315
references.citation: J Immunol. 2000 Dec 15;165(12):7096-101
references.pmid: 11120839
references.citation: Infect Immun. 2000 Nov;68(11):6398-401
references.pmid: 11035751
references.citation: J Immunol. 1999 Apr 1;162(7):3749-52
references.pmid: 10201887
references.citation: Science. 2001 Feb 23;291(5508):1544-7
references.pmid: 11222859
references.citation: Nat Med. 2003 May;9(5):525-32
references.pmid: 12692544
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5567-72
references.pmid: 11960013
references.citation: Semin Immunol. 2007 Feb;19(1):24-32
references.pmid: 17275323
references.citation: Semin Immunopathol. 2007 Apr;29(1):15-26
references.pmid: 17621951
references.citation: Eur J Immunol. 2003 Nov;33(11):2980-6
references.pmid: 14579266