Characterization of a novel DNA-sensing protein with links to innate immunity in planaria

Abstract

Schmidtea mediterranea is a planarian flatworm that is receiving growing attention as a model organism for immunological research due to its remarkable regenerative abilities, simple yet evolutionarily conserved immune system, and genetic tractability, offering insights into innate immunity and host-pathogen interactions. In an ongoing effort to identify and characterize components of the planarian innate immune system, the lab identified a potential sensor of foreign DNA that is called 2100. It seems to have evolved from a prokaryotic ATP nucleosidase protein called Cap 17 which is involved in a bacterial defense system and triggers bacterial cell death upon phage infection. This study shows that 2100 is essential for the survival of S. mediterranea since the knockdown of 2100 leads to progressive lesions and death of the organism. Despite having a lethal phenotype, there was no major change at the transcriptome level indicating that 2100 acts on the protein level. Potential interactors of 2100 were identified by immunoprecipitation followed by mass spectrometry proteomics. These data, together with super-resolution microscopy of 2100 localization as well as data from RNA sequencing, suggests that 2100 might act during endocytosis or autophagocytosis. Unfortunately, there are no established methods and assays for studying pathogen infections in planaria. Therefore, to take advantage of the extensive genetic toolset available in Drosophila, bacterial infection experiments were performed in flies with knockdown of 2100 in immune cells, suggesting a role of 2100 during innate immune system activation. 2100 is, therefore, likely a novel component of the invertebrate innate immune system with ancient roots in prokaryotic antiviral defense.