Sex-specific differences in the regulation and function of cellular immunity in Drosophila

Sex-specific differences in tissue growth and metabolism are prevalent in animals. It is also known that the immune response in humans differs between sexes and results in differential susceptibility of males and females to autoimmune diseases, malignancies, and infectious diseases. However, the mechanisms that mediate these sex-based differences in immunity are not well understood. Here, using the Drosophila hematopoietic organ, the lymph gland, which is the production site for immune cells in larva, we show that Drosophila exhibit sex-based differences in cellular immunity and investigate the mechanisms that underlie these differences. We found that compared to females, males exhibit smaller lymph glands, have less blood progenitors, and produce less immune cells. By manipulating sex in a tissue-specific manner we show that these sex specific differences are controlled by organ-specific mechanisms involving blood progenitors and their hematopoietic niche. Importantly, we find a sex-specific differential response to insulin signaling, an important regulator of the immune response in the niche. Finally, we provide evidence for differences in the cellular immune response following infection between males and females. Overall, our results provide mechanistic insight into how sex-differences in immunity are established.