STING mediates immune responses in the closest living relatives of animals

Abstract
Data availability
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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.

Data availability

Raw sequencing reads and normalized gene counts have been deposited at the NCBI GEO under accession GSE174340

The following data sets were generated

1. Woznica A
(2021) STING mediates immune responses in a unicellular choanoflagellate
NCBI Gene Expression Omnibus, GSE174340.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174340

The following previously published data sets were used

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JGI Monbr1.

https://mycocosm.jgi.doe.gov/Monbr1/Monbr1.home.html

Article and author information

Author details

Arielle Woznica

UT Southwestern Medical Center, Dallas, United States

For correspondence
Arielle.Woznica@UTSouthwestern.edu

Competing interests
The authors declare that no competing interests exist.
Ashwani Kumar

UT Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Carolyn R Sturge

UT Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6596-3356
Chao Xing

UT Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1838-0502
Nicole King

Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Julie K Pfeiffer

UT Southwestern Medical Center, Dallas, United States

For correspondence
Julie.Pfeiffer@UTSouthwestern.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2973-4895

Funding

Howard Hughes Medical Institute (Hanna Gray Fellows Program)

Arielle Woznica

Howard Hughes Medical Institute (Faculty Scholars Program)

Julie K Pfeiffer

Howard Hughes Medical Institute

Nicole King

Pew Charitable Trusts (Pew Innovation Fund)

Nicole King
Julie K Pfeiffer

Burroughs Wellcome Fund (Investigators in the Pathogenesis of Infectious Diseases)

Julie K Pfeiffer

National Cancer Institute (1P30 CA142543)

Arielle Woznica
Julie K Pfeiffer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.