Intercellular Communication Governs the Innate Immune Response of the Drosophila Intestinal Epithelium

Abstract

The Drosophila intestine is comprised of enterocytes (ECs), stem cells (ISCs), and enteroendocrine cells (EECs). Ubiquitously present in all three of the intestinal cell types, the immune deficiency (IMD) pathway plays a crucial role in mediating antimicrobial responses through a cascade that parallels the mammalian TNF signaling pathway. The key transcription factor responsible for activating the expression of antimicrobial peptide (AMP) genes in Drosophila is an NF-[x]B homolog named Relish. Preliminary studies from the Watnick Lab suggest an interplay between ECs and EECs within the Drosophila intestine in the context of innate immunity. Tachykinin (Tk) is an enteroendocrine peptide (EEP) expressed only in EECs, while AMPs are principally expressed in ECs. The unexpected reduction in AMP expression in ECs as a result of knocking down Tk led us to hypothesize that EEC-derived Tk regulates IMD signaling in ECs. On the other hand, decreased Tk expression observed when Relish was knocked down in ECs suggests the bidirectionality of this proposed intercellular innate immune communication. My project aimed to elucidate the mechanisms underlying Tk control of IMD pathway signaling in ECs. More specifically, by knocking down different components and known regulators of the IMD pathway in ECs, I sought to determine which are essential for IMD signaling in ECs in response to Tk. With the considerable similarity between Drosophila and human intestine with respect to innate immunity, we hope to contribute to the knowledge of how different intestinal cell types cooperate to elicit optimal antimicrobial responses with findings from this relatively simple but versatile insect model.