FIGURE

Fig. 7

ID

ZDB-FIG-220629-29

Publication

Roca et al., 2022 - Tumor necrosis factor induces pathogenic mitochondrial ROS in tuberculosis through reverse electron transport

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Fig. 7

Fig. 7. Currently available drugs can intercept TNF-induced mROS production and inhibit necrosis of mycobacterium-infected macrophages.

(A) Representative pseudocolored confocal images of 5-dpi granulomas in larvae with YFP-stained macrophages (green) that are wild-type or TNF^hi treated with diazoxide or vehicle, infected with red fluorescent Mm (magenta). Arrowheads, extracellular cording bacteria. Scale bar, 50 μm. (B to E) Bacterial cording in wild-type or TNF^hi larvae 5 days after infection with Mm, treated with vehicle or diazoxide (B), DM-malonate (C), telaglenastat (D), or perhexiline (E). *P < 0.05, **P < 0.01, ****P < 0.0001 (Fisher’s exact test). (F) Quantification of mROS in wild-type or TNF^hi larvae 1 day after infection with Mm, treated with metformin, phenformin, or vehicle. Horizontal bars denote means; **P < 0.01, ***P < 0.001 (one-way ANOVA with Tukey’s post-test). (G) Bacterial cording in wild-type or TNF^hi larvae 5 days after infection with Mm, treated with metformin or vehicle. ****P < 0.0001 (Fisher’s exact test). (H) Bacterial cording in wild-type larvae 5 days after infection with Mm, treated with vehicle or with succinate or DEBM alone or in combination with metformin. *P < 0.05, **P < 0.01, ***P < 0.001 (Fisher’s exact test). (I) Quantification of mROS in wild-type or TNF^hi 1 day after infection with Mtb, treated with metformin or vehicle. Horizontal bars denote means; *P < 0.05 (one-way ANOVA with Tukey’s post-test). (J) Percentage of dead THP-1 macrophages at 5 hours after addition of TNF, treated with metformin or vehicle starting 1 hour before TNF addition. Black and red symbols represent uninfected (ui) and Mtb-infected macrophages, respectively, within the same treatment well. Horizontal bars denote means; **P < 0.01, ****P < 0.0001 (one-way ANOVA with Tukey’s post-test). Data are representative of two independent experiments [(B) to (G) and (I)] or a single experiment [(H) and (J)].

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

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