Heightened immunopathological responses to LCMV-Clone 13 (Cl13) infection of mice with genetic or pharmacological inactivation of ABHD12. (a, b) Mortality plots for (a) AHBD12(+/+) and ABHD12(−/−) mice or (b) DO264 and (S)-DO271-treated mice (30 mg/kg, i.p., daily, dosing started one day prior to infection) monitored daily post-infection with Cl13. Data are pooled from at least three experiments with n=5 mice per group. For a, data are pooled from 3 independent experiments for a total of 22 ABHD12(+/+) and 25 ABHD12(−/−) mice. For b, the plot represents four experiments for a total of 28 (S)-DO271-treated mice and 30 DO264-treated mice. Two-side log-rank test was performed to compare two survival distributions. (c, d) Overall chemokine concentrations in BALF from (c) AHBD12(+/+) and ABHD12(−/−) mice or (d) DO264 and (S)-DO271-treated mice (30 mg/kg, i.p., daily, dosing started one day prior to infection) evaluated 10 days post-infection with Cl13. Data in c are data representative of two independent experiments of n=5 mice per group, and d are plots representative of mean values of three experiments of n=5 mice per group ± SEM. Two-sided Student’s t-test performed relative to ABHD12(+/+) or (S)-DO271-treated mice). (e) ABHD12(−/−) mice kill adoptively transferred splenocytes displaying LCMV-specific antigen (GP33-41) more efficiently than ABHD12(+/+) mice. In vivo killing of immunogenic LCMV-specific GP33-41 peptide or unrelated NP118-126-peptide-pulsed target cells labeled with high or low CellTrace Violet (CTV), respectively, was measured in spleen and lung tissue from ABHD12(+/+) and ABHD12(−/−) mice 7 days post-infection with Cl13. See Supplementary Fig. 29 for diagram of FACS gating strategy. Data represent of mean values of two independent experiments of n=5 mice per group ± SEM. Two-sided Student’s t-test performed relative to ABHD12(+/+) mice). (f) Cl13 viral titers were measured by plaque assay at the indicated days post-infection in either serum (left) or lung (right). Dotted lines indicate the limit of detection of the plaque assay. Two-sided Mann-Whitney U test was performed relative to ABHD12(+/+) data.