Immune Imaging Program, The Centenary Institute and the University of Sydney, New South Wales, Australia.
Autoimmunity, Transplantation and Inflammation (ATI) Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Immunol Cell Biol. 2021 Mar;99(3):299-308. doi: 10.1111/imcb.12410. Epub 2020 Nov 5.
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.
金黄色葡萄球菌是全球社区获得性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，我们生成了一种表达模型抗原的金黄色葡萄球菌菌株，以研究针对这种病原体的 T 细胞免疫反应的动态和幅度。我们证明金黄色葡萄球菌在皮内接种后立即通过淋巴液流被输送到引流淋巴结 (LN)。在那里，细菌通过激活 LN 常驻树突状细胞启动 CD8 细胞毒性 T 淋巴细胞 (CTL)增殖。大量中性粒细胞被招募到引流 LN 以吞噬细菌；然而，中性粒细胞耗竭并没有影响 CTL 增殖，尽管细菌负荷增加。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 细胞未能防止金黄色葡萄球菌的二次皮肤感染。我们的研究定义了金黄色葡萄球菌从皮肤的输送动力学，并表明 CTL 对于预防皮肤感染是可有可无的。
