Dissertations and Theses
Date of Award
2026
Document Type
Thesis
Department
Biology
First Advisor
Shubha Govind
Second Advisor
Rebecca Spokony
Third Advisor
Shireen Saleque
Keywords
Immune signaling, endocrine signaling, pesticide, Drosophila, tumors
Abstract
Juvenile hormone is needed at multiple stages for the proper development of an insect's life. It regulates metamorphosis and helps coordinate immune responses. Methoprene is an analog of juvenile hormone and a commonly used pesticide. Two transcription factor receptors in Drosophila mediate methoprene-induced signaling. Consistent with previous reports, we show that upon treatment with methoprene, mutant flies lacking functional juvenile hormone receptors can withstand the effects of methoprene and survive to adulthood. Methoprene treatment is known to induce the appearance of melanotic tumors in fly larvae. Considered similar to cellular immune reactions arising upon parasitoid wasp infection, we examined the cell types within these tumors and found them to be composed mainly of hemocytes called lamellocytes. Interestingly, while juvenile hormone receptor-deficient mutants are unable to form lamellocyte-containing melanotic tumors after methoprene treatment, these same mutants produce lamellocytes after parasitoid wasp attack and encapsulate wasp eggs. Encapsulation of wasp eggs is a cellular immune response that represents an acute inflammation reaction in insects. Because of the similarity of hemocyte types that make up methoprene-induced hematopoietic tumors and wasp induced capsules, we hypothesized that tumors in methoprene-treated animals form due to constitutive activation of immune signaling and thus represent a chronic inflammatory state of the animal. To test this idea, we genetically manipulated the levels of JAK-STAT and Toll-NF-kB pathway components to examine if blocking immune signaling in immune cells would reduce tumor penetrance in methoprene-treated animals. Here, we show that either ectopic expression of the wild type Toll-NF-kB inhibitor, the IkB homolog, cactus, or knockdown of Spätzle, Toll, or STAT in the fly’s immune system reduces tumor formation. Ectopic expression of cactus, and knockdown of Toll or Dorsal partially rescued the lethal effects of methoprene and some animals survived to adulthood. These results provide new insights into methoprene’s effects on the insect immune system and suggest that methoprene treatment in flies overrides normal immune-related regulatory feedback mechanisms. Its detrimental effects are due, in part, to excessive immune signaling arising from immune tissues. Whether and how the juvenile hormone pathway interacts with the immune signaling pathways remains to be examined. Continuous exposure to pesticides can be detrimental to human and animal health. Because the structures and functions of many immune genes in Drosophila are evolutionarily conserved in animals, our findings have implications in medicine and agriculture.
Recommended Citation
Luu, Thuan T., "Methoprene treatment induces systemic chronic inflammatory disease in Drosophila" (2026). CUNY Academic Works.
https://academicworks.cuny.edu/cc_etds_theses/1332
