4.8 Article

STING mediates immune responses in the closest living relatives of animals

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ELIFE
卷 10, 期 -, 页码 -

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eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.70436

关键词

choanoflagellates; Monosiga brevicollis; Pseudomonas aeruginosa; STING; Other

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资金

  1. Howard Hughes Medical Institute Hanna Gray Fellows Program
  2. Howard Hughes Medical Institute Faculty Scholars Program
  3. Howard Hughes Medical Institute
  4. Pew Charitable Trusts Pew Innovation Fund
  5. Burroughs Wellcome Fund
  6. National Cancer Institute [1P30 CA142543]

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Monosiga brevicollis, a choanoflagellate closely related to animals, exhibits innate immune responses to Pseudomonas aeruginosa, including STING activation and autophagic signaling induced by cyclic dinucleotides. These findings suggest a pre-animal role for STING in antibacterial immunity and establish M. brevicollis as a model system for studying immune responses.
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.

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