HLH-30/TFEB mediates sexual dimorphism in immunity in <i>caenorhabditis elegans</i>

Sexual dimorphism affects various biological functions, including immune responses. However, the mechanisms by which sex alters immunity remain largely unknown. Using <i>Caenorhabditis elegans</i> 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 <i>C. elegans</i>, males displayed increased activity of HLH-30/TFEB, which contributed to enhanced antibacterial immunity. <i>atg-2</i> (AuTophaGy (yeast Atg homolog) 2) upregulated by HLH-30/TFEB mediated increased immunity in male <i>C. elegans</i>. 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.