HLH-30/TFEB mediates sexual dimorphism in immunity in Caenorhabditis elegans

ABSTRACT

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

Abbreviations: atg-2: AuTophaGy (yeast Atg homolog) 2; FUDR: 5-fluoro-2’-deoxyuridine; GSEA: gene set enrichment analysis; HLH-30: Helix Loop Helix 30; LC3: 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

KEYWORDS:

• ATG-2/ATG2
• autophagy
• Caenorhabditis elegans
• HLH-30/TFEB
• pathogen resistance
• sexual dimorphism

Acknowledgements

We thank Caenorhabditis Genetics Center (CGC), National Bio-Resource Project (NBRP), and Dr. Dennis H. Kim for providing some C. elegans strains. We thank Dr. Malene Hansen, Dr. Chanhee Kang, and all the Lee lab members for comments on the manuscript and discussion.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All raw and processed sequencing data has been submitted to the NCBI Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE245430.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15548627.2024.2375779

Additional information

Funding

This workwas supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) NRF-2019R1A3B206774523 to S.-J.V.L.