IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice
IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice
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DOI：
10.1172/jci40891
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发表时间：
2010-05-01
影响因子：
15.9
通讯作者：
Miller, Lloyd S.
中科院分区：
文献类型：
--
作者：
Cho, John S.;Pietras, Eric M.;Miller, Lloyd S.
金黄色葡萄球菌是皮肤和软组织感染的最常见原因，迅速出现的耐药菌株正在造成严重的公共卫生问题。如果基于免疫的治疗是抗生素的替代品，需要更好地了解针对S的保护性免疫反应。金黄色葡萄球菌感染的皮肤。虽然中性粒细胞的募集是抗链球菌免疫所必需的。金黄色葡萄球菌，T细胞的作用已被提出。在这里，我们使用了S.金黄色葡萄球菌皮肤感染，以研究T细胞对宿主防御的贡献。我们发现，与野生型小鼠相比，缺乏γ δ T细胞但不缺乏α β T细胞的小鼠具有显著更大的皮肤病变，具有更高的细菌计数和受损的中性粒细胞募集。这种中性粒细胞募集依赖于表皮V γ 5（+）γ δ T细胞产生IL-17，但不依赖于IL-21和IL-22。此外，IL-17诱导需要IL-1、TLR 2和IL-23，并且对于宿主防御至关重要，因为IL-17 R缺陷小鼠具有与γ δ T细胞缺陷小鼠相似的表型。重要的是，γ δ T细胞缺陷小鼠接种S.金黄色葡萄球菌感染并用单剂量的重组IL-17处理的小鼠具有与WT小鼠相似的病变大小和细菌计数，表明IL-17可以恢复这些小鼠中受损的免疫力。我们的研究确定了我们认为产生IL-17的表皮γ δ T细胞在抗链球菌先天免疫中的新作用。金黄色皮肤感染。
Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in gamma delta but not alpha beta T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal V gamma 5(+) gamma delta T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R-deficient mice had a phenotype similar to that of gamma delta T cell-deficient mice. Importantly, gamma delta T cell-deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17-producing epidermal gamma delta T cells in innate immunity against S. aureus cutaneous infection.