Department of Nematology, University of California, Riverside, California, United States of America.
Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
PLoS Pathog. 2021 Oct 29;17(10):e1010027. doi: 10.1371/journal.ppat.1010027. eCollection 2021 Oct.
Parasitic nematodes cause significant morbidity and mortality globally. Excretory/secretory products (ESPs) such as fatty acid- and retinol- binding proteins (FARs) are hypothesized to suppress host immunity during nematode infection, yet little is known about their interactions with host tissues. Leveraging the insect parasitic nematode, Steinernema carpocapsae, we describe here the first in vivo study demonstrating that FARs modulate animal immunity, causing an increase in susceptibility to bacterial co-infection. Moreover, we show that FARs dampen key components of the fly immune response including the phenoloxidase cascade and antimicrobial peptide (AMP) production. Our data also reveal that FARs deplete lipid signaling precursors in vivo as well as bind to these fatty acids in vitro, suggesting that FARs elicit their immunomodulatory effects by altering the availability of lipid signaling molecules necessary for an efficient immune response. Collectively, these data support a complex role for FARs in immunosuppression in animals and provide detailed mechanistic insight into parasitism in phylum Nematoda.
寄生虫线虫在全球范围内导致了重大的发病率和死亡率。排泄/分泌产物（ESP），如脂肪酸和视黄醇结合蛋白（FAR），被假设在线虫感染期间抑制宿主免疫，但人们对它们与宿主组织的相互作用知之甚少。利用昆虫寄生线虫 Steinernema carpocapsae，我们在这里描述了第一个体内研究，证明 FAR 调节动物免疫，导致对细菌共感染的易感性增加。此外，我们表明 FAR 抑制了苍蝇免疫反应的关键成分，包括酚氧化酶级联和抗菌肽（AMP）的产生。我们的数据还表明，FAR 在体内消耗脂质信号前体，并在体外与这些脂肪酸结合，这表明 FAR 通过改变对有效免疫反应必不可少的脂质信号分子的可用性来发挥其免疫调节作用。总的来说，这些数据支持 FAR 在动物免疫抑制中的复杂作用，并为线虫门的寄生提供了详细的机制见解。
