Staphylococcal alpha-toxin is a strong inducer of interleukin-17 in humans.
Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus, with one-third of isolates producing alpha-toxin. Moreover, S. aureus colonization is positively correlated with the severity of eczema. Interleukin-17A (IL-17A) has gained attention in diseases associated with chronic skin infections. The aim of this study was to investigate the effects of sublytic alpha-toxin concentrations on IL-17A production. Sublytic alpha-toxin concentrations strongly induced IL-17A in peripheral blood mononuclear cells (PBMCs), isolated CD4(+) T cells, polarized Th17 cells, and Th17 clones from reactive atopy patch test lesions and blood from AD patients. Alpha-toxin induced IL-17A directly in T cells. The effect of alpha-toxin was further amplified by upregulation of IL-1 in monocytes. In conclusion, higher levels of IL-17A secretion induced by alpha-toxin in the skin partially explain how colonization with S. aureus can contribute to chronic skin inflammation.
Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany. niebuhr.margarete@mh-hannover.de
Margarete
M
Niebuhr
Merle
M
Gathmann
Helena
H
Scharonow
Diana
D
Mamerow
Susanne
S
Mommert
Hari
H
Balaji
Thomas
T
Werfel
D001427:Bacterial Toxins / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006460:Hemolysin Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013207:Staphylococcal Skin Infections / Q000150:complications* / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D007375:Interleukin-1; D020381:Interleukin-17; C021091:staphylococcal alpha-toxin
J Dermatol Sci. 2006 Sep;43(3):159-69
16887338
J Exp Med. 1995 Feb 1;181(2):747-53
7836926
Allergy. 2008 Jun;63(6):728-34
18445187
Biologics. 2009;3:303-18
19707417
Allergy. 2000 Jun;55(6):551-5
10858986
J Allergy Clin Immunol. 2006 Jul;118(1):3-21; quiz 22-3
16815133
J Allergy Clin Immunol. 2009 Jan;123(1):59-66.e4
19056110
J Leukoc Biol. 1999 May;65(5):665-70
10331496
Clin Exp Allergy. 2005 Aug;35(8):1088-95
16120092
Blood. 2010 Jan 21;115(3):530-40
19965648
J Allergy Clin Immunol. 2009 Mar;123(3):619-25
19281909
J Allergy Clin Immunol. 2000 Apr;105(4):820-6
10756235
Allergy. 2001 Nov;56(11):1034-41
11703215
J Allergy Clin Immunol. 2009 Jun;123(6):1244-52.e2
19439349
J Invest Dermatol. 2009 Aug;129(8):1878-91
19357709
Infect Immun. 1987 Jan;55(1):104-10
3025097
Microbiol Immunol. 2000;44(11):945-7
11145276
J Immunol. 1997 Mar 1;158(5):2500-5
9037002
Arch Dermatol. 1973 Apr;107(4):568-70
4697686
J Exp Med. 2009 Jun 8;206(6):1291-301
19487419
Allergy. 2009 Nov;64(11):1580-7
19392987
J Invest Dermatol. 2008 May;128(5):1207-11
18200064
Cell. 2006 Sep 22;126(6):1135-45
16990137
Infect Immun. 1989 Nov;57(11):3512-9
2807534
J Allergy Clin Immunol. 1992 Apr;89(4):801-10
1373161
Curr Opin Allergy Clin Immunol. 2007 Oct;7(5):374-81
17873575
Br J Dermatol. 1993 Jun;128(6):631-2
8338746
Br J Dermatol. 2002 Jul;147(1):55-61
12100185
J Immunol. 2009 Sep 15;183(6):3942-8
19717510
J Invest Dermatol. 2010 May;130(5):1373-83
20032993
J Clin Invest. 1993 Sep;92(3):1374-80
7690780
J Invest Dermatol. 1996 Oct;107(4):603-9
8823368
J Allergy Clin Immunol. 2003 Apr;111(4):875-81
12704372
J Invest Dermatol. 2008 Nov;128(11):2625-2630
18432274
Trends Immunol. 2006 Jan;27(1):17-23
16290228
Clin Microbiol Rev. 2000 Jan;13(1):16-34, table of contents
10627489
Nature. 2008 Apr 10;452(7188):773-6
18337720
J Immunol. 2007 Nov 15;179(10):6536-46
17982042
Br J Dermatol. 2009 Aug;161(2):300-5
19438853
Trends Immunol. 2010 Sep;31(9):354-61
20691634
Exp Dermatol. 2007 Feb;16(2):124-9
17222226
Infect Immun. 1994 Apr;62(4):1304-12
8132337
J Immunol. 1997 Aug 15;159(4):1909-16
9257856
J Am Acad Dermatol. 2005 Jul;53(1):67-72
15965423