(A) Timeline for mice infection and heart collection. Male and female wild-type and MLKL KO 6-to-8-week-old C57Bl/6 mice were intranasally infected with A/California/7/2009 (IAV) at day 0. Mice were euthanized and heart tissue was collected at day 12 (n = 10–12, 5–6 mice of each sex). (B) survival and (C) percent weight changes up to 10 days post IAV infection. (D) Viral titers were measured for WT C57Bl/6 and MLKL KO mice 12 days post initial IAV infection (n = 6, 3 of each sex) by the plaque assay and plotted in Log PFU/mL. (E) Levels of IFNƔ, TNF⍺, IFN⍺, IL-10, IFN-ƛ and IL-1-β measured by ELISA (pg/mL, n = 3–6, representative data for each sex of mice infected with IAV or challenged with vehicle (PBS) control). Log-rank (Mantel-Cox) test for survival. Kruskal-Wallis test with Dunn’s multiple-comparison post-test. Asterisks denote the level of significance observed: * = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤ 0.001.