The mammalian transcription factor TFEB and its Caenorhabditis elegans ortholog HLH-30 control the expression of genes encoding molecules involved in autophagy and lysosomal biogenesis in response to nutritional stress. In Immunity, Visvikis et al. show that HLH-30 drives the C. elegans transcriptional response to infection with Staphylococcus aureus. HLH-30-deficient worms show diminished survival after infection with S. aureus and other Gram-positive and Gram-negative bacteria, as well as diminished survival in response to starvation and diminished longevity in nonpathogenic conditions. HLH-30 controls the induction of regulators of longevity, such as insulin-signaling genes, which do not affect host defense, and antimicrobial and autophagy regulators, which are required for host immune responses but have no effect on longevity. During infection of mouse macrophages with S. aureus, TFEB is required for the expression of proinflammatory cytokines, such as IL-6, IL-1β and TNF, and chemokines. Thus, the antimicrobial and autophagy roles of these functional homologs are evolutionarily conserved.

Immunity 40, 896–909 (2014)