IL-22 derived from γδ T cells restricts Staphylococcus aureus infection of mechanically injured skin

详细信息    查看全文

• 作者：Nidhi Malhotra ; PhD^a ; ^&lowast ; ; Juhan Yoon ; PhD^a ; ^&lowast ; ; Juan Manuel Leyva-Castillo ; PhD^a ; ^&lowast ; ; Claire Galand ; PhD^a ; Nathan Archer ; MD ; PhD^b ; Lloyd S. Miller ; MD^b ; Raif S. Geha ; MD^a ; ^{Raif.geha@childrens.harvard.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：IL-22 ; S aureus ; neutrophils ; AD
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：138
• 期：4
• 页码：1098-1107.e3
• 全文大小：2525 K

文摘

Staphylococcus aureus is an opportunistic pathogen that colonizes the skin of patients with atopic dermatitis (AD) and aggravates their disease. Neutrophils and the cytokines IL-17A and IL-17F, which drive the expression of the neutrophil-attracting chemokines, are important for the clearance of S aureus infection. The cytokine IL-22 is often coproduced by IL-17–secreting cells. The levels of IL-22 are elevated in AD skin lesions.

Objective

We sought to determine the role of IL-22 in the clearance of S aureus infection of mouse skin subjected to tape stripping, a surrogate for scratching, a cardinal feature of AD.

Methods

S aureus was applied to the tape-stripped skin of wild-type and Il22^−/− mice. Bacterial burden was evaluated by enumerating colony-forming units. Quantitative PCR and ELISA were performed to quantify Il22 mRNA and IL-22 protein in mouse and human skin. Flow cytometry was used to enumerate neutrophils in the skin.

Results

Scratching the skin of healthy adults and tape stripping of mouse skin induced local expression of Il22 mRNA and IL-22 protein. Induction of Il22 expression by tape stripping was dependent on IL-23 and γδ T cells. Clearance of S aureus from tape-stripped skin was significantly impaired in Il22^−/− mice. Neutrophil infiltration and upregulation of expression of genes encoding the antimicrobial peptides antigen-6/urokinase-type plasminogen activator receptor related protein-1 and β-DEFENSIN 14 and the chemokine (C-X-C motif) ligand following tape stripping were significantly impaired in Il22^−/− mice.

Conclusions

These findings show that IL-22 is important for limiting the growth of S aureus on mechanically injured skin and caution that IL-23 and IL-22 blockade in patients with AD may enhance susceptibility to staphylococcal skin infection.