Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang 524023, China.
Int Immunopharmacol. 2020 Apr;81:106256. doi: 10.1016/j.intimp.2020.106256. Epub 2020 Feb 3.
Neutrophil extracellular traps (NETs) are consisted of DNA fibers and granular proteins and the formation of NETs has been identified as a crucial element of innate immune defense. IL-33 is a member of the IL-1 family cytokines and has been known as a strong trigger of type-2 immunity. Growing studies imply that IL-33 is involved in host defense against microbial infection. Here, we investigate the underlying influence of IL-33 on NET formation in mice with S. aureus cutaneous infection. We found that the level of IL-33 was significantly elevated in skin lesions of S. aureus-infected mice. The alarmin IL-33 inspired host innate defense through activation of NADPH oxidase to produce reactive oxygen species (ROS). Besides mediating the direct bactericidal activity within phagolysosomes, ROS production in IL-33-primed neutrophils was also critical for induction of NET formation. Enhancement of NET production by IL-33 contributed to ensnaring S. aureus and bacterial killing activity in vitro and in vivo. All together, these findings set up an IL-33/ST2 axis modulating NET generation, which strengthens host defense of innate immunity against S. aureus infection.
中性粒细胞胞外诱捕网（NETs）由 DNA 纤维和颗粒蛋白组成，其形成已被确定为先天免疫防御的关键因素。IL-33 是白细胞介素-1 家族细胞因子的一员，被认为是 2 型免疫的强触发因子。越来越多的研究表明，IL-33 参与宿主抵御微生物感染的防御。在这里，我们研究了 IL-33 在金黄色葡萄球菌皮肤感染小鼠中对 NET 形成的潜在影响。我们发现，金黄色葡萄球菌感染小鼠的皮肤损伤中 IL-33 的水平显著升高。警报素 IL-33 通过激活 NADPH 氧化酶产生活性氧（ROS）来激发宿主先天防御。ROS 除了在吞噬体中介导直接杀菌活性外，在 IL-33 引发的中性粒细胞中产生 ROS 对于诱导 NET 形成也至关重要。IL-33 增强 NET 形成有助于体外和体内捕获金黄色葡萄球菌并增强杀菌活性。总的来说，这些发现建立了一个 IL-33/ST2 轴调节 NET 生成的机制，增强了宿主先天免疫对金黄色葡萄球菌感染的防御能力。
