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Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster [Immunology and Inflammation]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-08-10 , DOI: 10.1073/pnas.2026554118
Crystal M Vincent 1, 2 , Marc S Dionne 1, 2
Affiliation  

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.



中文翻译:

IMD 信号的不同调节驱动黑腹果蝇感染病理学的性别差异 [免疫学和炎症]

雄性和雌性动物在感染结果方面表现出差异。性二态免疫的一种可能来源是免疫活动或病理学的性别特异性成本,但对于免疫与微生物诱导的病理学的独立影响以及这些是否可能因性别而异,我们知之甚少。在这里,通过测量具有野生型和突变免疫反应的黑腹果蝇的代谢和生理输出,我们测试了性别是否受到这些不同病理来源的不同影响,并确定了这种差异的关键调节因子。我们发现,两性表现出不同的免疫活性,但细菌衍生的代谢病理学相似。我们显示PGRP-LB的女性特异性免疫诱导表达,免疫缺陷 (IMD) 途径的负调节剂,使女性能够降低免疫活性以应对细菌数量的减少。在没有PGRP-LB的情况下,女性对感染的抵抗力更强,这证实了这一规定的功能重要性,并表明女性偏向的免疫限制是有代价的。

更新日期:2021-08-02
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