Antibody and DNA sensing pathways converge to activate the inflammasome during primary human macrophage infection.

ABSTRACT: Inflammasomes are potent innate immune signalling complexes that couple cytokine release with pro-inflammatory cell death. However, pathogens have evolved strategies to evade this cell autonomous system. Here, we show how antibodies combine with innate sensors in primary human macrophages to detect viral infection and activate the inflammasome. Our data demonstrate that antibody opsonisation of virions can activate macrophages in multiple ways. In the first, antibody binding of adenovirus causes lysosomal damage, activating NLRP3 to drive inflammasome formation and IL-1β release. Importantly, this mechanism enhances virion capture but not infection and is accompanied by cell death, denying the opportunity for viral replication. Unexpectedly, we also find that antibody-coated viruses, which

SUBMITTER: Labzin LI 

PROVIDER: S-EPMC6826209 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature