STING mediates immune responses in the closest living relatives of animals

Elife. 2021 Nov 3:10:e70436. doi: 10.7554/eLife.70436.

Abstract

Animals have evolved unique repertoires of innate immune genes and pathways that provide their first line of defense against pathogens. To reconstruct the ancestry of animal innate immunity, we have developed the choanoflagellate Monosiga brevicollis, one of the closest living relatives of animals, as a model for studying mechanisms underlying pathogen recognition and immune response. We found that M. brevicollis is killed by exposure to Pseudomonas aeruginosa bacteria. Moreover, M. brevicollis expresses STING, which, in animals, activates innate immune pathways in response to cyclic dinucleotides during pathogen sensing. M. brevicollis STING increases the susceptibility of M. brevicollis to P. aeruginosa-induced cell death and is required for responding to the cyclic dinucleotide 2'3' cGAMP. Furthermore, similar to animals, autophagic signaling in M. brevicollis is induced by 2'3' cGAMP in a STING-dependent manner. This study provides evidence for a pre-animal role for STING in antibacterial immunity and establishes M. brevicollis as a model system for the study of immune responses.

Keywords: Monosiga brevicollis; Pseudomonas aeruginosa; STING; choanoflagellates; evolutionary biology; infectious disease; microbiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Choanoflagellata / genetics
  • Choanoflagellata / immunology*
  • Choanoflagellata / metabolism
  • Choanoflagellata / microbiology
  • Cyclic GMP / metabolism
  • Immunity, Innate*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Pseudomonas Infections / immunology
  • Pseudomonas aeruginosa
  • Signal Transduction

Substances

  • Membrane Proteins
  • Cyclic GMP

Associated data

  • GEO/GSE174340