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Bacterial antigen is directly delivered to the draining lymph nodes and activates CD8+ T cells during Staphylococcus aureus skin infection
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2020-10-01 , DOI: 10.1111/imcb.12410
Gyohei Egawa 1 , Ben Roediger 1, 2 , Szun S Tay 1, 3 , Lois L Cavanagh 1 , Thomas V Guy 4 , Barbara Fazekas de 4 , Anthony J Brzoska 5 , Neville Firth 5 , Wolfgang Weninger 1, 6
Affiliation  

Staphylococcus aureus is one of the most common causes of community‐ and hospital‐acquired bacterial infection worldwide. While neutrophils play an important role in anti‐S. aureus immune defense, the role of adaptive immunity is less clear. In this study, we generated a model antigen‐expressing S. aureus strain to investigate the dynamics and magnitude of T cell immune responses against this pathogen. We demonstrate that S. aureus is delivered to the draining lymph nodes (LNs) by lymphatic flow immediately after intradermal inoculation. There, the bacterium initiates CD8+ cytotoxic T lymphocyte (CTL) proliferation via activating LN‐resident dendritic cells. Large numbers of neutrophils are recruited to the draining LNs to engulf bacteria; however, neutrophil depletion did not impact on CTL proliferation, despite increasing bacterial burden. Tissue‐resident memory T cells were formed in the skin at bacteria‐inoculated sites. Yet, blood and tissue‐resident memory T cells failed to prevent secondary cutaneous S. aureus infection. Our study defines the delivery kinetics of S. aureus from the skin and suggests that CTLs are dispensable for protection against skin infections.

中文翻译:

在金黄色葡萄球菌皮肤感染期间,细菌抗原被直接递送至引流淋巴结并激活 CD8+ T 细胞

金黄色葡萄球菌是全球社区和医院获得性细菌感染的最常见原因之一。虽然中性粒细胞在抗金黄色葡萄球菌免疫防御中发挥重要作用,但适应性免疫的作用尚不清楚。在这项研究中,我们生成了一个模型抗原表达金黄色葡萄球菌菌株,以研究针对该病原体的 T 细胞免疫反应的动力学和强度。我们证明金黄色葡萄球菌在皮内接种后立即通过淋巴流输送到引流淋巴结 (LN)。在那里,细菌启动 CD8 +通过激活 LN 驻留树突细胞促进细胞毒性 T 淋巴细胞 (CTL) 增殖。大量中性粒细胞被募集到引流的 LN 以吞噬细菌;然而,尽管增加了细菌负担,但中性粒细胞耗竭并未影响 CTL 增殖。组织驻留记忆 T 细胞在细菌接种部位的皮肤中形成。然而,血液和组织驻留记忆 T 细胞未能预防继发性皮肤金黄色葡萄球菌感染。我们的研究定义了金黄色葡萄球菌从皮肤的传递动力学,并表明 CTL 对于防止皮肤感染是可有可无的。
更新日期:2020-10-01
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