Fig. 8: LDHA is required for the PDCD6 deficiency-mediated enhancement of antibacterial effects.
From: PDCD6 regulates lactate metabolism to modulate LC3-associated phagocytosis and antibacterial defense
a–c Immunoblotting and gentamicin protection assays in LDHA-knockout (KO) THP-1 cells transduced with empty vector, Flag-tagged wild-type (WT) LDHA, or LDHA Y10F (a) and then challenged with L. monocytogenes (b) or S. Typhimurium (c). d, e Gentamicin protection assays in Pdcd6fl/fl and Pdcd6Δmye bone marrow-derived macrophages (BMDMs) pretreated or not with oxamic acid sodium salt (OAS) (10 μM) for 24 h, and then challenged with L. monocytogenes (d) or S. Typhimurium (e). f–h Immunoblotting and gentamicin protection assays in PDCD6-knockdown (KD)/LDHA-knockout (KO) THP-1 cells (f) transduced with empty vector, Flag-tagged WT LDHA, or LDHA Y10F following stimulation with L. monocytogenes (g) or S. Typhimurium (h). i–p Survival (i, m) (one-way ANOVA with multiple comparisons; Pdcd6Δmye vs. Pdcd6fl/fl, Pdcd6fl/fl OAS, and Pdcd6Δmye OAS; P = 0.0005 [(i, P = 0.0075 [(m]), body-weight changes (j, n) (one-way ANOVA with multiple comparisons; Pdcd6Δmye vs. Pdcd6fl/fl, Pdcd6fl/fl OAS, and Pdcd6Δmye OAS; P = 0.0003 [(j], P < 0.0001 [(n]), and bacterial loads in the liver (k, o) and spleen (l, p) of Pdcd6fl/fl and Pdcd6Δmye mice pretreated with OAS for 5 days, and then treated with L. monocytogenes (n = 6 per group, 3 males and 3 females) (i–l) or S. Typhimurium (n = 6 per group, 3 males and 3 females) (m–p) for the indicated periods. The averages of n = 4 (b–e, g, h) and n = 6 (i–p) biologically independent samples are shown. Data are shown as the mean ± SEM. Statistical significance was determined using one-way ANOVA with multiple comparisons in (g–p) and the t test (and nonparametric tests) in (b–e). The data presented in (a–p) are representative of three independent experiments.
