Persistent Activation of the Innate Immune Response in Adult Drosophila Following Radiation Exposure During Larval Development.
Cranial radiation therapy (CRT) is an effective treatment for pediatric central nervous system malignancies, but survivors often suffer from neurological and neurocognitive side effects that occur many years after radiation exposure. Although the biological mechanisms underlying these deleterious side effects are incompletely understood, radiation exposure triggers an acute inflammatory response that may evolve into chronic inflammation, offering one avenue of investigation. Recently, we developed a Drosophila model of the neurotoxic side effects of radiation exposure. Here we use this model to investigate the role of the innate immune system in response to radiation exposure. We show that the innate immune response and NF-ĸB target gene expression is activated in the adult Drosophila brain following radiation exposure during larval development, and that this response is sustained in adult flies weeks after radiation exposure. We also present preliminary data suggesting that innate immunity is radioprotective during Drosophila development. Together our data suggest that activation of the innate immune response may be beneficial initially for survival following radiation exposure but result in long-term deleterious consequences, with chronic inflammation leading to impaired neuronal function and viability at later stages. This work lays the foundation for future studies of how the innate immune response is triggered by radiation exposure and its role in mediating the biological responses to radiation. These studies may facilitate the development of strategies to reduce the deleterious side effects of CRT.
Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706.
Lisa J
LJ
Sudmeier
Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706.
Sai-Suma
SS
Samudrala
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792.
Steven P
SP
Howard
Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706 ganetzky@wisc.edu.
Barry
B
Ganetzky
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000528:radiation effects; D007113:Immunity, Innate; D007814:Larva / Q000528:radiation effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing
D029721:Drosophila Proteins; D016328:NF-kappa B
genetics of immunity; innate immunity; neuroinflammation; radioprotection; radiosensitivity