FBR: Javier Irazoqui

Speaker: Javier Irazoqui
UMass Chan Medical School, Department Microbiology, Worcester, Massachusetts, US

An organellar Fandango De A Tres in innate immunity

Talk abstract: Innate immune signaling is classically defined by pattern-recognition receptors (PRRs) that detect microbial products and trigger transcriptional responses, yet far less is understood about how intracellular organelles themselves participate in sensing infection and routing signals to the nucleus. Our recent work identifies peroxisomes as unexpected sentinels of bacterial invasion, capable of detecting pathogen-derived cues and initiating an organelle-to-organelle signaling cascade. We show that peroxisomes transmit these signals to lysosomes, which sequentially signal to the nucleus by activating a TFEB/TFE3-dependent transcriptional program that reconfigures host metabolism and antimicrobial defense, and promotes lysosomal and peroxisomal repair. This peroxisome-lysosome-nucleus dance reveals a previously unrecognized tier of innate immune regulation in which metabolic organelles integrate microbial detection with nuclear gene expression. Our findings establish organelle crosstalk as a critical—and previously underappreciated—component of the host response to bacterial pathogens.