Poxvirus dsDNA genomes differentially activate AIM2 or NLRP3 inflammasomes in human primary cells

ABSTRACT: The innate immune system is known for its ability to recognize cytosolic DNA as evidence of infection, but detailed studies of this process have been mostly limited to mice and cell lines. To investigate inflammasome responses in human primary cells, we used engineered viruses encoding the inflammasome reporter caspase-1CARD-EGFP. We show that released genomes of the model vaccinia and monkeypox poxviruses trigger robust inflammasome assembly in human primary cells. To determine the involved inflammasome sensors, we generated nanobodies against AIM2. Three of them inhibit AIM2 inflammasome assembly by blocking the polymerization of the AIM2 PYD domain, most potently as bivalent nanobodies. Utilizing an engineered vaccinia virus expressing bivalent AIM2 nanobodies, we demonstrate that infla

SUBMITTER: Yonas, M Tesfamariam 

PROVIDER: S-SCDT-10_1038-S44318-025-00690-Z | biostudies-other |

REPOSITORIES: biostudies-other