STING mediates immune responses in the closest living relatives of animals.

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 <i>Monosiga brevicollis</i>, one of the closest living relatives of animals, as a model for studying mechanisms underlying pathogen recognition and immune response. We found that <i>M. brevicollis</i> is killed by exposure to <i>Pseudomonas aeruginosa</i> bacteria. Moreover, <i>M. brevicollis</i> expresses STING, which, in animals, activates innate immune pathways in response to cyclic dinucleotides during pathogen sensing. <i>M. brevicollis</i> STING increases the susceptibility of <i>M. brevicollis</i> to <i>P. aeruginosa</i>-induced cell death and is required for responding to the cyclic dinucleotide 2'3' cGAMP. Furthermore, similar to animals, autophagic signaling in <i>M. brevicollis</i> 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 <i>M. brevicollis</i> as a model system for the study of immune responses.