Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE, 68198, USA.
J Neuroinflammation. 2012 Jun 15;9:128. doi: 10.1186/1742-2094-9-128.
Although IL-17A (commonly referred to as IL-17) has been implicated in the pathogenesis of central nervous system (CNS) autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R) knockout (KO) mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25). In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT) cell and gamma-delta (γδ) T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT) animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.
虽然白细胞介素-17A（通常称为白细胞介素-17）已被牵连到中枢神经系统（CNS）自身免疫性疾病的发病机制中，但它在中枢神经系统细菌感染中的作用仍不清楚。为了评估白细胞介素-17 家族成员在中枢神经系统感染背景下的更广泛影响，我们利用缺乏对白细胞介素-17、白细胞介素-17F 和白细胞介素-17E（白细胞介素-25）反应能力的白细胞介素-17 受体（IL-17R）敲除（KO）小鼠。在本文中，我们证明 IL-17R 信号调节金黄色葡萄球菌诱导的脑脓肿形成过程中的细菌清除以及自然杀伤 T（NKT）细胞和γ-δ（γδ）T 细胞浸润。具体来说，与野生型（WT）动物相比，IL-17R KO 小鼠在金黄色葡萄球菌感染后第 7 天和第 14 天表现出更高的细菌负荷。此外，IL-17R KO 动物显示出升高的中性粒细胞趋化因子产生，揭示了补偿缺乏 IL-17R 活性的能力。尽管存在这些差异，但 IL-17R KO 和 WT 小鼠的固有免疫细胞向脑脓肿的募集相似，而 IL-17R 信号对适应性免疫细胞的募集有更大的影响。特别是，在感染后第 7 天，IL-17R KO 小鼠中的γδ T 细胞流入增加。此外，在 IL-17R KO 动物的脑脓肿中不存在 NK1.1high 浸润，而且令人惊讶的是，在未感染的 IL-17R KO 小鼠的肝脏中很少检测到。尽管白细胞介素-17 是其他感染模型中中性粒细胞的关键调节剂，但我们的数据表明 IL-17R 信号在调节中枢神经系统细菌感染期间的适应性免疫方面起着重要作用。
