DIFFERENT BUT COMPLEMENTARY ROLES OF RNASET2 AND AIF-1 IN THE MODULATION OF MEDICINAL LEECHES INNATE IMMUNE RESPONSE

Several studies demonstrated that RNASET2 (Ribonuclease T2) and AIF-1 (Allograft Inflammatory Factor-1) regulate the activation and modulation of innate immune response in both vertebrates and invertebrates. Even if it is known that these proteins are involved in macrophages recruitment and that their expression significantly increases after bacterial infections, the mechanisms by which they regulate the inflammatory response are still poorly defined. In order to explore the links between RNASET2 and AIF1 and their interrelation during innate immune response, here we focus our research on the effect of LPS (bacterial lipopolysaccharides) injection on their expression in the medicinal leech. This invertebrate is a well-established experimental model for studying innate immunity, given its very simple anatomy and its marked similarity with vertebrates in inflammatory processes. Our results, obtained by prokaryotic-eukaryotic co-cultures and in vivo infection model, show that RNASET2 and AIF-1 play a crucial role in orchestrating a functional cross-talk between granulocytes and macrophages. RNASET2 is first released by granulocytes, playing an early antibacterial role. Subsequently, RNASET2-recruited macrophages expressing AIF-1, which, in turn, chemoattracts other macrophages to further sustain the anti-bacterial inflammatory response. The final result is the activation of a marked and effective response against pathogen infection.