The Role of Drosophila Toll Receptors in the Central Nervous System

Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that play pivotal roles in innate immunity by detecting pathogen-associated molecular patterns. While initially characterized for their function in dorsoventral patterning and antifungal defense in Drosophila, the Toll family is now understood to have undergone a functional expansion in the nervous system. This review synthesizes the current understanding of the nine Drosophila Toll receptors (Toll-1 to Toll-9) and their roles in the central nervous system (CNS). We discuss how these receptors, particularly through non-canonical signaling pathways, function as neurotrophin receptors and cell surface recognition molecules. They mediate a wide range of cellular processes, from axon guidance to synaptic partner matching and the regulation of neuronal survival versus apoptosis through the competitive recruitment of adaptor proteins such as dMyD88 and Sarm. We further explore the involvement of Toll signaling in adult brain structural plasticity, sleep homeostasis, and behavioral responses to environmental stressors such as ethanol. Importantly, this article addresses the context-dependent duality of Toll signaling in neuropathology, dysregulation, and aberrant activation, which are closely related to neurodegeneration, lifespan determination, and infection responses. Through this timely summary of current research, this review highlights the molecular switches that govern Toll receptor functional states and their roles in neuro-immune interactions, with implications for understanding neurological diseases in vertebrates.