Litomosoides sigmodontis microfilariae-induced eosinophil ETosis is dependent on the canonical inflammasome pathway.

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.