A NOVEL NOX/PHOX-CD38-NAADP-TFEB AXIS IMPORTANT FOR MACROPHAGE ACTIVATION DURING BACTERIAL PHAGOCYTOSIS
Mehran Najibi, Havisha H. Honwad, Joseph A. Moreau, Stephanie M. Becker, Javier E. Irazoqui
Abstract
chelation and PPP3/calcineurin inhibition prevented TFEB activation by phagocytosis and ROS (reactive oxygen species), impairing the induction of pro-inflammatory cytokines such as IL6 and TNF/TNFα. Therefore, here we describe a previously unknown pathway that links phagocytosis with macrophage pro-inflammatory polarization via TFEB and related transcription factor TFE3. These findings reveal that activation of TFEB and TFE3 is a key regulatory event for the activation of macrophages, and have important implications for infections, inflammation, cancer, obesity, and atherosclerosis.
Topics & Concepts
TFEBPhagocytosisBiologyCell biologyBasic helix-loop-helix leucine zipper transcription factorsNADPH oxidaseTranscription factorReactive oxygen speciesMacrophageRespiratory burstBiochemistryIn vitroGeneDNA-binding proteinCalcium signaling and nucleotide metabolismAdenosine and Purinergic SignalingAutophagy in Disease and Therapy