期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：32
DOI：10.1073/pnas.2026554118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Sex differences in infection outcome are a widely observed phenomenon. While it is known that biological sex can influence an animal’s response to infection, the mechanisms through which these differences emerge are less clear. Here, we describe a mechanism through which heightened regulation of the IMD signaling pathway by female—but not male—
Drosophila melanogaster reduces the cost of immune activity at the expense of resistance to bacterial infection. Through the masculinization of the main organ responsible for antimicrobial peptide activity in the fly (fat body), this work demonstrates that this heightened immune regulation is mediated by sex-determining pathways.
Male and female animals exhibit differences in infection outcomes. One possible source of sexually dimorphic immunity is the sex-specific 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 female-specific 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.
