Clearance of Staphylococcus aureus Nasal Carriage Is T Cell Dependent and Mediated through Interleukin-17A Expression and Neutrophil Influx
Clearance of Staphylococcus aureus Nasal Carriage Is T Cell Dependent and Mediated through Interleukin-17A Expression and Neutrophil Influx
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DOI：
10.1128/iai.00084-13
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发表时间：
2013-06-01
影响因子：
3.1
通讯作者：
Shirtliff, Mark E.
中科院分区：
文献类型：
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作者：
Archer, Nathan K.;Harro, Janette M.;Shirtliff, Mark E.
人的前鼻孔是金黄色葡萄球菌定殖的主要储库。大约20%的健康人群是持续性的，80%是间歇性的。鼻腔内的金黄色葡萄球菌。以前的研究表明，S。金黄色葡萄球菌鼻携带和增加的医院感染风险，以及由于免疫功能障碍而增加的携带。然而，允许持续存在或介导S.金黄色葡萄球菌对鼻粘膜的作用是根本不确定的。在这项研究中，我们在C57 BL/6 J小鼠中建立了一个携带模型，并表明接种后14天开始清除。相比之下，具有缺陷的适应性免疫应答的SCID小鼠不能消除S。金黄色葡萄球菌，即使在接种后28天。此外，通过分别评价T细胞受体β/δ（TCR-β/δ）敲除（KO）和IgH-mu KO小鼠的携带清除率，发现去殖民化是T细胞介导的，但不依赖于B细胞。细胞因子白细胞介素1 β（IL-1 β）、KC（也称为CXC配体1 [CXCL 1]）和IL-17 A的上调发生在接种鼻内S.金黄色。IL-17 A的产生对于清除至关重要，因为IL-17 A缺陷小鼠不能有效地清除S。金黄色马车。随后，从野生型和IL-17 A缺陷型定殖小鼠获得的鼻灌洗液中评价细胞分类计数。这些计数显示IL-17 A依赖性中性粒细胞迁移。抗体介导的中性粒细胞在定殖小鼠中的耗竭导致清除率降低，与同种型处理的对照组相比。我们的数据表明，Th 17相关的免疫应答是鼻非殖民化所必需的。这种应答是T细胞依赖性的，并通过IL-17 A产生和中性粒细胞流入介导。Th 17相关的免疫应答可能是减轻持续性链球菌远端感染的策略的目标。金黄色葡萄球菌携带情况。
The anterior nares of humans are the major reservoir for Staphylococcus aureus colonization. Approximately 20% of the healthy human population is persistently and 80% is intermittently colonized with S. aureus in the nasal cavity. Previous studies have shown a strong causal connection between S. aureus nasal carriage and increased risk of nosocomial infection, as well as increased carriage due to immune dysfunction. However, the immune responses that permit persistence or mediate clearance of S. aureus on the nasal mucosa are fundamentally undefined. In this study, we developed a carriage model in C57BL/6J mice and showed that clearance begins 14 days postinoculation. In contrast, SCID mice that have a deficient adaptive immune response are unable to eliminate S. aureus even after 28 days postinoculation. Furthermore, decolonization was found to be T cell mediated but B cell independent by evaluating carriage clearance in T-cell receptor beta/delta (TCR-beta/delta) knockout (KO) and IgH-mu KO mice, respectively. Upregulation of the cytokines interleukin 1 beta (IL-1 beta), KC (also termed CXC ligand 1 [CXCL1]), and IL-17A occurred following inoculation with intranasal S. aureus. IL-17A production was crucial for clearance, since IL-17A-deficient mice were unable to effectively eliminate S. aureus carriage. Subsequently, cell differential counts were evaluated from nasal lavage fluid obtained from wild-type and IL-17A-deficient colonized mice. These counts displayed IL-17A-dependent neutrophil migration. Antibody-mediated depletion of neutrophils in colonized mice caused reduced clearance compared to that in isotype-treated controls. Our data suggest that the Th17-associated immune response is required for nasal decolonization. This response is T cell dependent and mediated via IL-17A production and neutrophil influx. Th17-associated immune responses may be targeted for strategies to mitigate distal infections originating from persistent S. aureus carriage in humans.