HLH-30/TFEB mediates sexual dimorphism in immunity in <italic>Caenorhabditis elegans</italic>.

Sexual dimorphism affects various biological functions, including immune responses. However, the mechanisms by which sex alters immunity remain largely unknown. Using <italic>Caenorhabditis elegans</italic> as a model species, we showed that males exhibit enhanced immunity against various pathogenic bacteria through the upregulation of HLH-30 (Helix Loop Helix 30/TFEB (transcription factor EB)), a transcription factor crucial for macroautophagy/autophagy. Compared with hermaphroditic <italic>C. elegans</italic>, males displayed increased activity of HLH-30/TFEB, which contributed to enhanced antibacterial immunity. <italic>atg-2</italic> (AuTophaGy (yeast Atg homolog) 2) upregulated by HLH-30/TFEB mediated increased immunity in male <italic>C. elegans</italic>. Thus, the males appear to be equipped with enhanced HLH-30/TFEB-mediated autophagy, which increases pathogen resistance, and this may functionally prolong mate-searching ability with reduced risk of infection.<bold>Abbreviations:</bold> <italic>atg-2</italic>: AuTophaGy (yeast Atg homolog) 2; FUDR: 5-fluoro-2’-deoxyuridine; GSEA: gene set enrichment analysis; HLH-30: Helix Loop Helix 30; <italic>LC3</italic>: microtubule associated protein 1 light chain 3; NGM: nematode growth media; RNA-seq: RNA sequencing; SEM: standard error of the mean; TFEB: transcription factor EB; WT: wild-type [ABSTRACT FROM AUTHOR]