C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5−/− mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5−/− mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c+ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

中文翻译：

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CCR5 介导的 NK 细胞向肾脏募集是宿主防御系统性白色念珠菌感染的关键步骤

CC 趋化因子受体 5 (CCR5) 调节各种免疫细胞向感染部位的运输。在本研究中，我们发现全身性白色念珠菌感染后肾脏中 CCR5 及其配体的表达迅速增加，感染 CCR5−/− 小鼠的死亡率和发病率增加，表明 CCR5 有助于有效防御全身性念珠菌的机制. 白色念珠菌感染。CCR5-/- 小鼠对白色念珠菌感染的易感性是由于真菌清除能力受损，进而导致肾脏炎症和损伤加剧。响应于白色念珠菌感染，CCR5 介导的 NK 细胞募集到肾脏是中性粒细胞（主要杀真菌效应细胞）的抗微生物活性所必需的。从机制上讲，C. 白色念珠菌诱导 CD11c+ 树突状细胞 (DC) 表达 IL-23。IL-23 反过来通过 NK 细胞产生 GM-CSF 来增强中性粒细胞的杀真菌活性。由于 GM-CSF 增强了 IL-23 的产生以响应白色念珠菌，NK 细胞和 DC 之间形成的正反馈回路似乎起到了宿主防御放大点的作用。总之，我们的结果表明，CCR5 介导的 NK 细胞募集到真菌感染部位是重要的一步，是对全身性白色念珠菌感染的先天抵抗的基础。NK 细胞和 DC 之间形成的正反馈回路似乎起到了宿主防御放大点的作用。总之，我们的结果表明，CCR5 介导的 NK 细胞募集到真菌感染部位是重要的一步，是对全身性白色念珠菌感染的先天抵抗的基础。NK 细胞和 DC 之间形成的正反馈回路似乎起到了宿主防御放大点的作用。总之，我们的结果表明，CCR5 介导的 NK 细胞募集到真菌感染部位是重要的一步，是对全身性白色念珠菌感染的先天抵抗的基础。