Unraveling the Immune Metabolic Epigenetic Axis to Improve Tuberculosis Therapy

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dc.contributorHanke, Marc H.
dc.contributorNishiguchi, Tomoki
dc.contributorDiNardo, Andrew
dc.contributor.authorLadki, Malik S.
dc.date.accessioned2021-02-24T22:43:48Z
dc.date.available2021-02-24T22:43:48Z
dc.date.issued2020-09-29
dc.description.abstractTuberculosis is caused by the bacteria Mycobacterium tuberculosis (Mtb), which mainly affects the lungs. Macrophages (MΦ) are critical innate immune cells that phagocytize and kill Mtb. Prior studies have shown that the metabolic enzymes of the tricarboxylic acid cycle (TCA) “moonlight” in the nucleus and regulate cell function and fate by acting as epigenetic switches to regulate cell phenotype. We have evaluated if the moonlighting of TCA enzymes regulates MΦ immune phenotype. MΦ can develop “trained” phenotypes with improved anti-mycobacterial immunity while “tolerant” MΦ develops phenotypes with detrimental anti-mycobacterial immunity. We hypothesized that both “trained” and “Tolerant” MΦ phenotypes are dependent upon TCA moonlighting. Using monocyte-derived macrophages (MDMΦ) and standard protocols to induce trained or tolerant MΦ, we implemented confocal microscopy to quantify TCA moonlighting and used flow cytometry to measure to cytokine production. Median fluorescent intensity (MFI) of Isocitrate dehydrogenase3 (IDH3) and citrate synthase (CS) in the nuclei of MDMΦ was determined. The effect on phenotype and TCA moonlighting by inhibitors of multiple pathways were evaluated. Both trained and tolerant protocols induced TCA moonlighting of IDH3 and CS (p<0.05). Trained phenotype exhibited an increase in cytokine production, while the tolerant phenotype demonstrated a decrease in cytokine production. This project was completed with contributions from Tomoki Nishiguchi and Andrew R. DiNardo from Baylor College of Medicine.
dc.description.departmentBiology and Biochemistry, Department of
dc.description.departmentHonors College
dc.identifier.urihttps://hdl.handle.net/10657/7610
dc.language.isoen_US
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.titleUnraveling the Immune Metabolic Epigenetic Axis to Improve Tuberculosis Therapy
dc.typePoster

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