Figure 6
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- ZDB-FIG-191230-1309
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- Roca et al., 2019 - TNF Induces Pathogenic Programmed Macrophage Necrosis in Tuberculosis through a Mitochondrial-Lysosomal-Endoplasmic Reticulum Circuit
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Pharmacological Inhibition of Voltage-Gated L-Type Ca2+ Channels Inhibits TNF-Mediated Macrophage Mitochondrial Ca2+ Overload and Necrosis in Mm- and Mtb-Infected Larvae (A) Percentage of Rhod-2-positive macrophages in 1 dpi control or TNF-high larvae treated with nifedipine, verapamil, or diltiazem. Horizontal bars, means; ∗∗p < 0.01; ∗∗∗p < 0.001 (one-way ANOVA with Tukey’s post-test). Representative of 2 independent experiments. (B–D) Cording in 5 dpi control or TNF-high larvae treated with nifedipine (B), diltiazem (C), and verapamil (D). ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001 (Fisher’s exact test). Representative of 2–4 independent experiments. (E) Representative confocal images of 1 dpi larvae with yellow fluorescent macrophages infected with 100 WT Mm or 80 Mtb (both red fluorescent). Scale bar, 50 μm. (F) Quantitation of mitochondrial ROS production in infected macrophages of 1 dpi TNF-high or control larvae infected with 100 WT Mm or 80 Mtb. Horizontal bars, means; ∗∗∗p < 0.001 (one-way ANOVA with Tukey’s post-test). (G) Quantitation of mitGCaMP3 fluorescence in infected macrophages in 1 dpi TNF-high or control larvae infected with 100 WT Mm or 185–200 Mtb treated with dantrolene, nifedipine, diltiazem, or verapamil. Horizontal bars, means; ∗∗∗p < 0.001 (one-way ANOVA with Tukey’s post-test). |
Reprinted from Cell, 178(6), Roca, F.J., Whitworth, L.J., Redmond, S., Jones, A.A., Ramakrishnan, L., TNF Induces Pathogenic Programmed Macrophage Necrosis in Tuberculosis through a Mitochondrial-Lysosomal-Endoplasmic Reticulum Circuit, 1344-1361.e11, Copyright (2019) with permission from Elsevier. Full text @ Cell