The Transcription Factors TFEB and TFE3 Link the FLCN-AMPK Signaling Axis to Innate Immune Response and Pathogen Resistance.

Cell reports (2019-03-28)
Leeanna El-Houjeiri, Elite Possik, Tarika Vijayaraghavan, Mathieu Paquette, José A Martina, Jalal M Kazan, Eric H Ma, Russell Jones, Paola Blanchette, Rosa Puertollano, Arnim Pause
RESUMEN

TFEB and TFE3 are transcriptional regulators of the innate immune response, but the mechanisms regulating their activation upon pathogen infection are poorly elucidated. Using C. elegans and mammalian models, we report that the master metabolic modulator 5'-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN) act upstream of TFEB/TFE3 in the innate immune response, independently of the mTORC1 signaling pathway. In nematodes, loss of FLCN or overexpression of AMPK confers pathogen resistance via activation of TFEB/TFE3-dependent antimicrobial genes, whereas ablation of total AMPK activity abolishes this phenotype. Similarly, in mammalian cells, loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression. Importantly, a rapid reduction in cellular ATP levels in murine macrophages is observed upon lipopolysaccharide (LPS) treatment accompanied by an acute AMPK activation and TFEB nuclear localization. These results uncover an ancient, highly conserved, and pharmacologically actionable mechanism coupling energy status with innate immunity.

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Monoclonal Anti-α-Tubulin antibody produced in mouse, clone DM1A, ascites fluid
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Benzamidine, ≥95.0%
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Anti-TFE3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
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EPA 8260A Surrogate Standards Mix, certified reference material, 2000 μg/mL each component in methanol
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MISSION® esiRNA, targeting human FLCN
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