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.
Highlights
Innate immunity is the first line of defense against pathogens for all animals, in which it is crucial for distinguishing between self and non-self, recognizing and responding to pathogens, and repairing cellular damage
Quantifying images revealed that Atg8+ puncta accumulate after 2’3’ cGAMP treatment in wild type, but not STING– cells (Figure 6G). These results suggest that M. brevicollis responds to 2’3’ cGAMP through STING-dependent induction of the autophagy pathway
We screened diverse bacteria to identify a choanoflagellate pathogen, and determined that M. brevicollis is killed by sustained exposure to P. aeruginosa bacteria
Summary
Innate immunity is the first line of defense against pathogens for all animals, in which it is crucial for distinguishing between self and non-self, recognizing and responding to pathogens, and repairing cellular damage. Many gene families that play critical roles in animal innate immune responses 49 are unique to animals[3] Comparing animals with their closest relatives, the choanoflagellates, can provide unique insights into the ancestry of animal immunity and reveal other key 52 features of the first animal, the ‘Urmetazoan’[4,5,6]. Several innate immune pathway genes once considered to be animal-specific are present in choanoflagellates, including cGAS and STING, both of which are crucial for innate responses to cytosolic DNA in 58 animals (Figure 1- Supplement 1)[3,9,10]. STING domain-containing systems are present in bacteria where they may contribute to anti-phage defense[22,23], raising the possibility that eukaryotic STING-like proteins were acquired from lateral 72 gene transfer[24]. Brevicollis, thereby expanding our understanding of the pre-metazoan ancestry of STING signaling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
