Fig. 2: LdhaLysM−/− mice are more susceptible to TB. | Nature Communications

Fig. 2: LdhaLysM−/− mice are more susceptible to TB.

From: NAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis

Fig. 2

A Depiction of the favored conversion of pyruvate to lactate by LDH composed predominantly of LDHA subunits compared to the reverse reaction by LDH composed predominantly of LDHB subunits. B Depiction of the glycolytic defect imposed by LDHA deletion. C Immunoblot showing relative LDHA protein levels in LDHA−/− and LDHAfl/fl BMDMs. D LDHA protein levels and (E) LDH function in protein lysates normalized to the mean values for LDHAfl/fl BMDMs. Symbols represent biological replicates from an independent experiment (n = 4/group). F ECAR of LDHAfl/fl and LDHA−/− BMDMs. Dashed lines indicate the injection of glucose, oligomycin, and 2-DG. Symbols and error bars represent mean ± SEM of 5 technical replicates. G Columns, error bars, and symbols represent the mean, SEM, and individual values for glycolytic capacity determined from data in (F). H Kaplan-Meier plot of mice infected with ~30 CFU of Mtb (n = 11/group). I Box plot of Mtb burden in mouse lungs, where the center, upper and lower hinges, and upper and lower whiskers indicate the 2nd quartile, 3rd and 1st quartile, and ±1.5 times the interquartile range (3rd quartile – 1st quartile), respectively. Symbols represent biological replicates pooled from two independent experiments (n ≥ 10/group). J H&E staining of representative lung sections from Mtb-infected mice (n = 6 per group from one experiment) at indicated times post infection. K Normalized histograms representing cellular density around each nucleus in a tissue section. Within each timepoint, biological replicates were ranked by mean density and plotted with the replicate of the corresponding rank from the other genotype. L Cumulative histogram of all replicates compared by genotype at each time point. Percentages indicate the proportion of cells in each group above a threshold density of 25. Data in (D) and (E) are shown as individual values with the group mean ± SEM. Statistical significance was determined by two-sided, two-sample t-test not assuming equal variance (D, E, G); log-rank test (H); two-sided, two-sample Wilcoxon rank-sum test (I); and two-sample z-test (L). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; exact p-values for each comparison are listed in Supplementary Data 1. Source data are provided as a Source Data file.

Back to article page