Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
J Immunol. 2020 Dec 1;205(11):3122-3129. doi: 10.4049/jimmunol.1901482. Epub 2020 Oct 19.
IL-17D is a cytokine that belongs to the IL-17 family and is conserved in vertebrates and invertebrates. In contrast to IL-17A and IL-17F, which are expressed in Th17 cells, IL-17D is expressed broadly in nonimmune cells. IL-17D can promote immune responses to cancer and viruses in part by inducing chemokines and recruiting innate immune cells such as NK cells. Although bacterial infection can induce IL-17D in fish and invertebrates, the role of mammalian IL-17D in antibacterial immunity has not been established. To determine whether IL-17D has a role in mediating host defense against bacterial infections, we studied i.p. infection by group A (GAS) in wild-type (WT) and mice. Compared with WT animals, mice deficient in IL-17D experienced decreased survival, had greater weight loss, and showed increased bacterial burden in the kidney and peritoneal cavity following GAS challenge. In WT animals, IL-17D transcript was induced by GAS infection and correlated to increased levels of chemokine CCL2 and greater neutrophil recruitment. Of note, GAS-mediated IL-17D induction in nonimmune cells required live bacteria, suggesting that processes beyond recognition of pathogen-associated molecular patterns were required for IL-17D induction. Based on our results, we propose a model in which nonimmune cells can discriminate between nonviable and viable GAS cells, responding only to the latter by inducing IL-17D.
白细胞介素 17D（IL-17D）是一种细胞因子，属于白细胞介素 17 家族，在脊椎动物和无脊椎动物中都有保守性。与在 Th17 细胞中表达的白细胞介素 17A 和白细胞介素 17F 不同，白细胞介素 17D 广泛表达于非免疫细胞中。白细胞介素 17D 可以通过诱导趋化因子和招募先天免疫细胞（如自然杀伤细胞）来促进对癌症和病毒的免疫反应。尽管细菌感染可以诱导鱼类和无脊椎动物产生白细胞介素 17D，但哺乳动物白细胞介素 17D 在抗细菌免疫中的作用尚未确定。为了确定白细胞介素 17D 是否在介导宿主对细菌感染的防御中发挥作用，我们研究了野生型（WT）和 小鼠的腹腔内（i.p.）感染 A 组链球菌（GAS）的情况。与 WT 动物相比，缺乏白细胞介素 17D 的小鼠在 GAS 攻击后生存率降低，体重减轻更多，肾脏和腹腔中的细菌负荷增加。在 WT 动物中，GAS 感染诱导了白细胞介素 17D 的转录，并与趋化因子 CCL2 水平的升高和中性粒细胞的募集增加相关。值得注意的是，非免疫细胞中 GAS 介导的白细胞介素 17D 诱导需要活细菌，这表明除了识别病原体相关分子模式之外，还需要其他过程来诱导白细胞介素 17D。基于我们的结果，我们提出了一个模型，即非免疫细胞可以区分无活力和有活力的 GAS 细胞，仅对后者通过诱导白细胞介素 17D 做出反应。
