Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis.
BACKGROUND
Staphylococcus aureus is a well known trigger factor of atopic dermatitis (AD). Besides the superantigens, further exotoxins are produced by S. aureus and may have an influence on the eczema.


OBJECTIVE
To explore the impact of staphylococcal alpha-toxin on human T cells, as those represent the majority of skin infiltrating cells in AD.


METHODS
Adult patients with AD were screened for cutaneous colonization with alpha-toxin producing S. aureus. As alpha-toxin may induce necrosis, CD4(+) T cells were incubated with sublytic alpha-toxin concentrations. Proliferation and up-regulation of IFN-gamma on the mRNA and the protein level were assessed. The induction of t-bet translocation in CD4(+) T cells was detected with the Electrophoretic Mobility Shift Assay.


RESULTS
Thirty-four percent of the patients were colonized with alpha-toxin producing S. aureus and alpha-toxin was detected in lesional skin of these patients by immunohistochemistry. Sublytic alpha-toxin concentrations induced a marked proliferation of isolated CD4(+) T cells. Microarray analysis indicated that alpha-toxin induced particularly high amounts of IFN-gamma transcripts. Up-regulation of IFN-gamma was confirmed both on the mRNA and the protein level. Stimulation of CD4(+) T cells with alpha-toxin resulted in DNA binding of t-bet, known as a key transcription factor involved into primary T helper type 1 (Th1) commitment.


CONCLUSIONS
alpha-toxin is produced by S. aureus isolated from patients with AD. We show here for the first time that sublytic alpha-toxin concentrations activate T cells in the absence of antigen-presenting cells. Our results indicate that alpha-toxin is relevant for the induction of a Th1 like cytokine response. In AD, this facilitates the development of Th1 cell dominated chronic eczema.
Breuer
K
K
Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany. breuer.kristine@mh-hannover.de
Wittmann
M
M
Kempe
K
K
Kapp
A
A
Mai
U
U
Dittrich-Breiholz
O
O
Kracht
M
M
Mrabet-Dahbi
S
S
Werfel
T
T
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009336:Necrosis / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000382:microbiology; D012874:Skin Diseases, Infectious / Q000276:immunology / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000276:immunology*; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D010738:Type C Phospholipases / Q000096:biosynthesis* / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D000098815:T-bet Transcription Factor
D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma; D010738:Type C Phospholipases