Ehrens Alexandra, Lenz Benjamin, Nieto-Pérez Celia, Latz Eicke, Schmidt Florian I, Hoerauf Achim, Hübner Marc P
Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.
Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, Germany.
Cell Rep. 2025 Jan 28;44(1):115164. doi: 10.1016/j.celrep.2024.115164. Epub 2025 Jan 7.
Granulocytes exert several effector mechanisms, including the release of DNA traps during ETosis. While bacteria-induced ETosis has been linked to the non-canonical inflammasome pathway, the role of the inflammasome activation during ETosis in response to extracellular pathogens has not been investigated. The current study demonstrates that microfilariae (MF) of the rodent filarial nematode Litomosoides sigmodontis induce eosinophil ETosis via the canonical inflammasome pathway. The absence of key components of the canonical inflammasome, including gasdermin D, caspase-1, the adaptor molecule ASC, or AIM2 (double-stranded DNA sensor) prevents MF-induced DNA release in murine eosinophils. While AIM2 activation is not affecting other effector mechanisms such as reactive oxygen species generation and nuclear membrane collapse, it appears to be critical in mediating the release of DNA from the cell during the later stages of ETosis. Finally, the findings on inflammasome-dependent ETosis in response to MF are confirmed in human eosinophils.
粒细胞发挥多种效应机制，包括在嗜酸性粒细胞胞外陷阱形成（ETosis）过程中释放DNA陷阱。虽然细菌诱导的ETosis与非经典炎性小体途径有关，但ETosis过程中炎性小体激活对细胞外病原体的反应作用尚未得到研究。当前研究表明，啮齿动物丝虫线虫巴西日圆线虫的微丝蚴（MF）通过经典炎性小体途径诱导嗜酸性粒细胞ETosis。经典炎性小体的关键成分缺失，包括gasdermin D、半胱天冬酶-1、衔接分子ASC或AIM2（双链DNA传感器），可阻止MF诱导的小鼠嗜酸性粒细胞DNA释放。虽然AIM2激活不影响其他效应机制，如活性氧生成和核膜塌陷，但它似乎在ETosis后期介导细胞DNA释放中起关键作用。最后，在人类嗜酸性粒细胞中证实了对MF的炎性小体依赖性ETosis的研究结果。
