Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster

Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is the sexspecific costs of immune activity or pathology, but little is known about the independent effects of immune- versus microbe-induced pathology and whether these may differ for the sexes. Here, by measuring metabolic and physiological outputs in Drosophila melanogaster with wild-type and mutant immune responses, 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 femalespecific immune-inducible expression of PGRP-LB, a negative regulator of the immune deficiency (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 to infection, confirming the functional importance of this regulation and suggesting that female-biased immune restriction comes at a cost.

Automated summary

Male and female animals show differences in infection outcomes, with potential sources of sexually dimorphic immunity being the sex-specific costs of immune activity or pathology. This study found that males and females exhibit differential immune activity but similar bacteria-derived metabolic pathology, with females having a female-specific immune-inducible expression of PGRP-LB which plays a critical role in reducing immune activity in response to bacterial reductions.