Disparate regulation of imd drives sex differences in infection tolerance in Drosophila melanogaster

Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is sex-specific costs of immune activity or pathology, but little is known about the independent effects of immune-induced versus microbe-induced pathology, and whether these may differ for the sexes. Here, through measuring metabolic and physiological outputs in wild-type and immune-compromised , we test whether the sexes are differentially impacted by these various sources of pathology. We find that in the fruit fly, the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of , a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of this regulator, females are more resistant of infection, indicating that female-biased immune restriction comes at a cost. These data suggest that male and female flies exhibit broadly similar abilities to resist infection, but females exhibit greater tolerance of infection as a result of increased immune regulation.