Toll-like receptors in skin infections and inflammatory diseases.
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.
Lai
Yuping
Y
Division of Dermatology, University of California, San Diego, Dermatology Section, VA San Diego Healthcare System, San Diego, California 92161, USA.
Gallo
Richard L
RL
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*
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D051193:Toll-Like Receptors
Science. 1998 Dec 11;282(5396):2085-8
9851930
Nat Rev Immunol. 2003 Feb;3(2):169-76
12563300
J Biol Chem. 2003 Oct 24;278(43):41702-8
12871942
J Biol Chem. 2003 Jul 4;278(27):24526-32
12721283
Science. 2004 Mar 5;303(5663):1522-6
15001781
J Clin Invest. 2004 May;113(10):1473-81
15146245
Nat Immunol. 2006 Feb;7(2):139-47
16378096
World J Gastroenterol. 2006 Apr 14;12(14):2149-60
16610014
Nature. 2007 Jun 21;447(7147):972-8
17538624
Nat Immunol. 2004 Oct;5(10):1052-60
15334086
Nature. 2007 Oct 4;449(7162):564-9
17873860
J Immunol. 2003 Sep 15;171(6):3154-62
12960343
Arch Pathol Lab Med. 2003 Feb;127(2):178-86
12562231
Annu Rev Immunol. 2004;22:181-215
15032578
Nat Immunol. 2004 May;5(5):503-7
15064760
Science. 2003 Aug 1;301(5633):640-3
12855817
Blood. 2006 Jan 15;107(2):610-8
16174756
J Infect Dis. 1998 Aug;178(2):551-5
9697742
J Biol Chem. 2004 Apr 23;279(17):17079-84
14764599
Nature. 1996 Oct 3;383(6599):443-6
8837778
Clin Microbiol Rev. 2008 Jan;21(1):13-25
18202435
J Invest Dermatol. 1998 May;110(5):734-9
9579537
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8222-6
9653168
J Rheumatol. 2002 Jun;29(6):1176-82
12064831
Nature. 1998 Mar 19;392(6673):245-52
9521319
J Immunol. 2004 Sep 1;173(5):2913-7
15322147
Science. 1997 Oct 31;278(5339):866-9
9346485
Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15416-21
15492225
Annu Rev Immunol. 2003;21:335-76
12524386
J Biol Chem. 2001 Oct 5;276(40):37692-9
11477091
Nat Rev Immunol. 2001 Nov;1(2):135-45
11905821
Biochem Biophys Res Commun. 2002 Nov 29;299(2):216-21
12437972
Int J Lepr. 1965 Jul-Sep;33(3):Suppl:533-41
5892587
Nat Immunol. 2001 Aug;2(8):675-80
11477402
Semin Immunol. 2007 Feb;19(1):41-7
17280841
J Exp Med. 1998 Sep 7;188(5):985-90
9730900
Curr Pharm Des. 2006;12(32):4215-28
17100624
Curr Pharm Des. 2006;12(32):4123-34
17100615
Immunol Rev. 2004 Dec;202:8-32
15546383
Clin Exp Allergy. 2006 Aug;36(8):1049-62
16911361
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3533-8
14982987
Mol Cell Biol. 2002 Oct;22(20):7158-67
12242293
J Invest Dermatol. 2008 Apr;128(4):816-24
17943182
Immunity. 2006 Jan;24(1):79-91
16413925
Nat Immunol. 2005 Aug;6(8):769-76
15995707
J Interferon Cytokine Res. 2003 Jan;23(1):13-23
12639295
J Infect Dis. 2005 Mar 1;191(5):746-8
15688290
J Neurochem. 2005 Jul;94(2):289-98
15998280
Br J Dermatol. 2003 Apr;148(4):670-9
12752123
J Immunol. 2000 Nov 15;165(10):5392-6
11067888
J Biol Chem. 2003 Dec 12;278(50):49751-62
14519765
Arch Dermatol Res. 2006 Jan;297(7):280-8
16283346
Eur J Immunol. 2004 Mar;34(3):796-805
14991609
J Immunol. 2007 Feb 1;178(3):1829-34
17237433
J Exp Med. 2003 Oct 6;198(7):1043-55
14517278
Br J Dermatol. 2005 Dec;153(6):1105-13
16307644
Eur J Immunol. 2006 Jan;36(1):199-206
16323247
J Clin Invest. 1985 Oct;76(4):1427-35
2997278
Nature. 2001 Oct 18;413(6857):732-8
11607032
Immunol Rev. 2000 Apr;174:192-209
10807517
Nat Immunol. 2004 Oct;5(10):987-95
15454922
J Leukoc Biol. 2001 May;69(5):691-7
11358975
Nature. 2001 Sep 6;413(6851):78-83
11544529
Clin Exp Immunol. 2006 Apr;144(1):1-9
16542358
Eur J Immunol. 2001 Nov;31(11):3131-7
11745329
N Engl J Med. 1998 Aug 20;339(8):520-32
9709046
J Virol. 2005 Mar;79(5):2910-9
15709010
Nat Immunol. 2001 Sep;2(9):835-41
11526399
Science. 1999 Oct 15;286(5439):420-1
10577203
J Immunol. 1999 Sep 1;163(5):2821-8
10453027
J Immunol. 2002 Dec 15;169(12):6668-72
12471095
Cell. 1997 Jul 25;90(2):373-83
9244310
Science. 1997 Oct 31;278(5339):860-6
9346484
Science. 2004 May 14;304(5673):1014-8
15143282
J Exp Med. 1998 Feb 16;187(4):461-8
9463396
J Leukoc Biol. 2000 Apr;67(4):508-14
10770283
J Immunol. 2002 Aug 1;169(3):1535-41
12133981
Curr Opin Immunol. 2002 Feb;14(1):103-10
11790539
J Exp Med. 2000 Oct 2;192(7):1069-74
11015447
J Invest Dermatol. 2007 Feb;127(2):331-41
17068485
J Immunol. 2001 Nov 15;167(10):5887-94
11698465
Nat Immunol. 2004 Feb;5(2):190-8
14716310
Trends Immunol. 2003 Jun;24(6):286-90
12810098
FASEB J. 2008 Jul;22(7):2168-76
18263703
Cell. 2006 Feb 24;124(4):783-801
16497588
Nat Immunol. 2004 Oct;5(10):975-9
15454920
Nat Immunol. 2001 Oct;2(10):947-50
11547333
J Immunol. 2004 Apr 15;172(8):4987-94
15067080
J Biol Chem. 2003 Mar 14;278(11):8869-72
12527755
Nat Rev Immunol. 2004 Jul;4(7):512-20
15229470
J Immunol. 2000 Dec 1;165(11):6308-13
11086067
J Exp Med. 2004 Jun 21;199(12):1631-40
15197227
Am J Respir Cell Mol Biol. 2004 Oct;31(4):463-9
15242847
J Immunol. 2004 Jul 15;173(2):1179-83
15240708
Cell. 1996 Sep 20;86(6):973-83
8808632
J Mol Med (Berl). 2002 Sep;80(9):549-61
12226737
J Immunol. 2003 Oct 15;171(8):4304-10
14530355
Arthritis Rheum. 2004 May;50(5):1686-9
15146440
Curr Opin Immunol. 2006 Feb;18(1):24-30
16337365
Curr Pharm Des. 2006;12(32):4135-42
17100616
Nat Immunol. 2003 Feb;4(2):161-7
12539043
J Am Acad Dermatol. 2006 Jun;54(6):951-83; quiz 983-6
16713451
Nat Med. 1999 Jun;5(6):702-5
10371511
J Biol Chem. 2007 Jun 22;282(25):18265-18275
17400552
Int Immunol. 2006 Jul;18(7):1115-26
16728430
Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13831-6
16954184
Cell. 1997 Oct 17;91(2):243-52
9346241
Int Immunol. 2005 Jan;17(1):1-14
15585605
Semin Cutan Med Surg. 2005 Jun;24(2):73-8
16092794
J Immunol. 2007 Nov 15;179(10):7110-20
17982103
Drug Discov Today. 2007 Jan;12(1-2):80-7
17198976
Annu Rev Immunol. 2000;18:621-63
10837071
Int Immunol. 2006 Feb;18(2):355-62
16373361
Nature. 2002 Apr 18;416(6882):750-6
11923871
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18631-5
18006661
Immunity. 1999 Oct;11(4):443-51
10549626
Nature. 1997 Jul 24;388(6640):394-7
9237759
Annu Rev Immunol. 2000;18:767-811
10837075
N Engl J Med. 2002 Oct 10;347(15):1151-60
12374875
Science. 2006 Mar 24;311(5768):1770-3
16497887
J Biol Chem. 2001 Nov 9;276(45):41661-7
11518704
Immunology. 2005 Apr;114(4):531-41
15804290
Nature. 2002 Jan 24;415(6870):389-95
11807545
Microbes Infect. 2006 May;8(6):1513-21
16697678
J Biol Chem. 2003 May 9;278(19):16713-9
12609980
Nature. 2003 Nov 6;426(6962):33-8
14603309
Infect Immun. 2001 Mar;69(3):1477-82
11179315
J Immunol. 2000 Dec 15;165(12):7096-101
11120839
Infect Immun. 2000 Nov;68(11):6398-401
11035751
J Immunol. 1999 Apr 1;162(7):3749-52
10201887
Science. 2001 Feb 23;291(5508):1544-7
11222859
Nat Med. 2003 May;9(5):525-32
12692544
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5567-72
11960013
Semin Immunol. 2007 Feb;19(1):24-32
17275323
Semin Immunopathol. 2007 Apr;29(1):15-26
17621951
Eur J Immunol. 2003 Nov;33(11):2980-6
14579266