Abstract 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 Drosophila melanogaster , we test whether the sexes are differentially impacted by these various sources of pathology and identify a critical regulator of this difference. We find that the sexes exhibit differential immune activity but similar bacteria-derived metabolic pathology. We show that female-specific immune-inducible expression of PGRP-LB , a negative regulator of the Imd pathway, enables females to reduce immune activity in response to reductions in bacterial numbers. In the absence of PGRP-LB , females are more resistant of infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.

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