Nlrp3 inflammasome activation and Gasdermin D-driven pyroptosis are immunopathogenic upon gastrointestinal norovirus infection
Fig 4
STAT1 suppresses the secretion of mature IL-1β from unprimed MNV-infected macrophages through inhibiting MAVS-mediated pro-IL-1β induction.
(A-C) Unprimed bone-marrow-derived macrophages (BMDM) from Stat1+/- and Stat1-/- littermates were mock infected (control) or infected with either UV-inactivated or live MNV, both at a MOI 5. After 24 hours (A) culture supernatants were analyzed for secreted IL-1β by ELISA; (B) cell lysates were immunoblotted for IL-1β, caspase-1, and GSDMD processing; and (C) at indicated time points MNV genome copy numbers in BMDMs were determined. (D-E) Unprimed bone-marrow-derived macrophages (BMDM) from Stat1+/-, Stat1-/- and Stat1-/-Mavs-/- mice were mock infected (control) or infected with either UV-inactivated or live MNV, both at a MOI 5. After 24 hours (D) supernatant was analyzed for secreted IL-1β levels by ELISA; and (E) cell lysates were immunoblotted for IL-1β and caspase-1 processing. Data shown in (A, D) are the means ± SD of triplicate wells from a representative experiment out of two independent experiments. Data shown in (B, E) are representative for 2 independent experiments. Data shown in (D) represent means ± SD of BMDMs derived from three mice per genotype, analyzed in three independent experiments, each with triplicate wells.