Circadian-Shaped Immune Variability Predicts Infection Outcome

Authors

Jonathan Lalsiamthara
Mariko Locke
Alejandro Aballay

Publication Date

1-2-2026

Journal

Science Advances

DOI

10.1126/sciadv.adx8112

PMID

41477859

PMCID

PMC12757043

PubMedCentral® Posted Date

1-1-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Disease risk and severity are influenced by genetics, epigenetics, and environmental factors. However, immune responses vary even among genetically similar or related individuals, shaped by inherited and noninherited factors. Using Caenorhabditis elegans, we found that pathogen susceptibility can be predicted by preinfection biomarkers. Individuals with high-basal expression of irg-5, an infection response gene regulated by the p38 mitogen-activated protein kinase-1 (PMK-1) pathway, were more susceptible to Pseudomonas aeruginosa infection. A genome-wide screen identified the myeloid ecotropic viral integration site-1 (MEIS) homeobox protein UNC-62 as a regulator of irg-5 expression, acting through PMK-1 and GATA binding erythroid-like transcription factor (ELT-2). Further analysis revealed that maternal circadian timing shaped offspring immune heterogeneity and inhibition of clock genes eliminated the effects induced by maternal timing. These findings highlight circadian-driven immune variability as a potential adaptive strategy for resilience against infection.

Keywords

Animals, Caenorhabditis elegans Proteins, Caenorhabditis elegans, Circadian Rhythm, Pseudomonas aeruginosa, Pseudomonas Infections, p38 Mitogen-Activated Protein Kinases, Transcription Factors, Gene Expression Regulation, Biomarkers, Mitogen-Activated Protein Kinases

Published Open-Access

yes

Recommended Citation

Jonathan Lalsiamthara, Mariko Locke, and Alejandro Aballay, "Circadian-Shaped Immune Variability Predicts Infection Outcome" (2026). Faculty, Staff and Student Publications. 181.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/181