ILANIT 2023

Allogeneic response and cellular immune function in Planarians

Eliya Sultan 1 Chew Chai 2 Shany Barkan 1 Shani Talice 1 Aner Ottolenghi 1 Uzi Hadad 1 Orly Gershuni-Yahalom 1 Bo Wang 2 Benyamin Rosental 1
1Microbiology, Immunology, and Genetics, Ben Gurion University of the Negev, Israel
2Bioengineering, Stanford University, USA

Allogeneic responses appear in several invertebrates, and we found them also in planarians. Segments from different planarians were fused to form a chimera. While the most of syngeneic chimera survived, about half of the allogeneic chimera did not survive, apparently due to inflammatory reactions. To test cellular allogeneic responses in planarians, we used cells transplantations and ex-vivo assays. Results from ex-vivo assays show that the allogeneic response is not based on the direct recognition of foreign cells. It is not affecting cytotoxicity or phagocytosis on the allogeneic or xenogeneic levels. Interestingly, we found that activin2 is affecting the in-vivo chimeras rejection through the inflammatory process. On the cellular level, we show that exposure to recombinant activin2 increase cytotoxicity and cell phagocytosis. Using cytoskeleton inhibitions, different cellular and protein concentrations, and pre-treatments we validated that the activin2 protein is mediating cellular function. The results of the cellular cytotoxicity indicates that the cytotoxic cells do not require a specific cellular conjugation to be activated through specific recognition (“level 2 cytotoxicity”), but are activated through general inflammatory signals and kill cells in its vicinity (“level 1 cytotoxicity”), this is more resembling human neutrophils which release toxic granules to the environment. These results corroborate our and others suggestion that cytotoxicity level 1 predates the specific cytotoxicity of level 2.