biostudies-otherUnknownDr. Larisa, I LabzinEuropean Molecular Biology Organization (EMBO)UK Research and Innovation | Medical Research Council (MRC)Department of Health | National Health and Medical Research Council (NHMRC)Wellcome Trust (WT)The EMBO Journalhttps://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMBOJ-2018-101365Inflammasomes 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 opsonization 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-1? 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, whichbiostudies-otherGNT1124612ALTF 1487-2015U105181010Dr. Larisa, I LabzinDr. Marina VaysburdDr. Stian FossDr. Jan, Terje AndersenDr. Leo, C JamesDr. Maria BottermannMr. Pablo Rodriguez-SilvestreDr. Dean CliftfalseAntibody and DNA sensing pathways activate the inflammasome during human macrophage infection.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 opsonization 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-1? 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, which2020-02-24T21:00:28Z2020-02-24T21:00:28Z2020-02-24T21:00:28ZS-SCDT-EMBOJ-2018-10136510.15252/embj.2018101365