Immunity-longevity tradeoff neurally controlled by GABAergic transcription factor PITX1/UNC-30

Benson Otarigho, Alejandro Aballay

Research output: Contribution to journalArticlepeer-review

Abstract

A body of evidence indicates that metazoan immune and aging pathways are largely interconnected, but the mechanisms involved in their homeostatic control remain unclear. In this study, we find that the PITX (paired-like homeodomain) transcription factor UNC-30 controls the tradeoff between immunity and longevity from the nervous system in Caenorhabditis elegans. PITX/UNC-30 functional loss enhances immunity in a GATA/ELT-2- and p38 MAPK/PMK-1-dependent manner and reduced longevity by activating MXD/MDL-1 and the C2H2-type zinc finger transcription factor PQM-1. The immune inhibitory and longevity stimulatory functions of PITX/UNC-30 require the sensory neuron ASG and a signaling pathway controlled by NPR-1, which is a G protein-coupled receptor related to mammalian neuropeptide Y receptors. Our findings uncover a suppressive role of GABAergic signaling in the neural control of a biological tradeoff where energy is allocated toward immunity at the expense of longevity.

Original languageEnglish (US)
Article number109187
JournalCell Reports
Volume35
Issue number8
DOIs
StatePublished - May 25 2021

Keywords

  • C. elegans
  • GABAergic
  • P. aeruginosa
  • immunity
  • infection
  • innate
  • longevity
  • neuropeptides
  • neurotransmitters
  • tradeoff

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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