STING mediates immune responses in the closest living relatives of animals
- UT Southwestern Medical Center, United States
- Howard Hughes Medical Institute, University of California, Berkeley, United States
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
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STING mediates immune responses in a unicellular choanoflagellateNCBI Gene Expression Omnibus, GSE174340.
Article and author information
Author details
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.
Reviewing Editor
- Sara Cherry, University of Pennsylvania, United States
Version history
- Preprint posted: May 14, 2021 (view preprint)
- Received: May 17, 2021
- Accepted: November 2, 2021
- Accepted Manuscript published: November 3, 2021 (version 1)
- Version of Record published: November 15, 2021 (version 2)
Copyright
© 2021, Woznica et al.
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.
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STING mediates immune responses in the closest living relatives of animals
eLife 10:e70436.
https://doi.org/10.7554/eLife.70436
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Copy number variation in large gene families is well characterized for plant resistance genes, but similar studies are rare in animals. The zebrafish (Danio rerio) has hundreds of NLR immune genes, making this species ideal for studying this phenomenon. By sequencing 93 zebrafish from multiple wild and laboratory populations, we identified a total of 1513 NLRs, many more than the previously known 400. Approximately half of those are present in all wild populations, but only 4% were found in 80% or more of the individual fish. Wild fish have up to two times as many NLRs per individual and up to four times as many NLRs per population than laboratory strains. In contrast to the massive variability of gene copies, nucleotide diversity in zebrafish NLR genes is very low: around half of the copies are monomorphic and the remaining ones have very few polymorphisms, likely a signature of purifying selection.
