| Citation | El-Houjeiri L, Possik E, Vijayaraghavan T, Paquette M, Martina JA, Kazan JM, Ma EH, Jones R, Blanchette P, Puertollano R, Pause A. The Transcription Factors TFEB and TFE3 Link the FLCN-AMPK Signaling Axis to Innate Immune Response and Pathogen Resistance. Cell Rep, 2019. |
| PubMed ID | 30917316 |
| Short Description | The Transcription Factors TFEB and TFE3 Link the FLCN-AMPK Signaling Axis to Innate Immune Response and Pathogen Resistance. GEO Record: GSE128029 Platform: GPL11346 Download gene-centric, log2 transformed data: WBPaper00056471.ce.mr.csv |
| # of Conditions | 8 |
Full Description
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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 ofTFEB/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. Experimental Details: WBPaper00056471:N2_rep4 WBPaper00056471:N2_rep3 WBPaper00056471:N2_rep2 WBPaper00056471:N2_rep1 WBPaper00056471:flcn-1(ok975)_rep4 WBPaper00056471:flcn-1(ok975)_rep3 WBPaper00056471:flcn-1(ok975)_rep2 WBPaper00056471:flcn-1(ok975)_rep1. |
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