Cigarette Smoke Extract Exposure Affects Innate Immune Response, Metabolic Rate, and Locomotor Activity of Drosophila melanogaster

PURPOSE: Cigarette smoke (CS) disrupts innate immune homeostasis through oxidative stress and inflammatory signaling, contributing to respiratory diseases such as asthma and COPD. Because Drosophila melanogaster shares approximately 75% of disease-related human genes and possesses a well-characterized innate immune system without confounding adaptive responses, it represents a tractable model for investigating smoke-induced pathology. METHODS: This study examined the effects of developmental cigarette smoke extract (CSE) exposure on innate immune activation, locomotor activity, and metabolic rate in Drosophila melanogaster. RESULTS: Larvae exposed to 10-50% CSE exhibited dose-dependent increases in crystal-cell activation and melanized wound area, indicating heightened innate immune responsiveness likely driven by CSE-induced oxidative stress and hematopoietic dysregulation. Locomotor activity, assessed by negative geotaxis, was impaired at moderate concentrations in both sexes, with females showing greater sensitivity at lower doses, reflecting sex-specific differences. Metabolic rate measurements revealed a significant hypermetabolic response exclusively in male flies at 50% CSE, consistent with an elevated oxidative detoxification burden and vulnerability in males. CONCLUSION: Collectively, these findings demonstrate that CSE elicits a coordinated physiological stress response integrating immune activation with behavioral and metabolic dysfunction. This work supports Drosophila melanogaster as a translational model for dissecting the systemic consequences of smoke-induced innate immune dysregulation.