The gastrointestinal (GI) nematode Strongyloides stercoralis (S.s.) causes human strongyloidiasis, a potentially life-threatening disease that currently affects over 600 million people globally. The uniquely pernicious aspect of S.s. infection, as compared to all other GI nematodes, is its autoinfective larval stage (L3a) that maintains a low-grade chronic infection, allowing undetectable persistence for decades. Infected individuals who are administered glucocorticoid therapy can develop a rapid and often lethal hyperinfection syndrome within days. Hyperinfection patients often present with dramatic increases in first- and second-stage larvae and L3a in their GI tract, with L3a widely disseminating throughout host organs leading to sepsis. How glucocorticoid administration drives hyperinfection remains a critical unanswered question; specifically, it is unknown whether these steroids promote hyperinfection through eliminating essential host protective mechanisms and/or through dysregulating parasite development. This current deficiency in understanding is largely due to the previous absence of a genetically defined mouse model that would support all S.s. life-cycle stages and the lack of successful approaches for S.s. genetic manipulation. However, there are currently new possibilities through the recent demonstration that immunodeficient NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG) mice support sub-clinical infections that can be transformed to lethal hyperinfection syndrome following glucocorticoid administration. This is coupled with advances in transcriptomics, transgenesis, and gene inactivation strategies that now allow rigorous scientific inquiry into S.s. biology. We propose that combining in vivo manipulation of host immunity and deep immunoprofiling strategies with the latest advances in S.s. transcriptomics, piggyBac transposon-mediated transgene insertion, and CRISPR/Cas-9-mediated gene inactivation will facilitate new insights into the mechanisms that could be targeted to block lethality in humans with S.s. hyperinfection.

胃肠道 (GI) 线虫粪类圆线虫( Ss ) 会导致人类类圆线虫病，这是一种可能危及生命的疾病，目前影响全球超过 6 亿人。Ss独特的有害方面与所有其他胃肠道线虫相比，感染是其自身感染的幼虫阶段（L3a），可维持低度慢性感染，数十年无法检测到。接受糖皮质激素治疗的感染者可在数日内迅速发展成致命的重度感染综合征。重度感染患者的胃肠道中第一和第二阶段幼虫和 L3a 的数量通常会急剧增加，其中 L3a 在整个宿主器官中广泛传播，导致败血症。糖皮质激素给药如何导致过度感染仍然是一个悬而未决的关键问题。具体而言，尚不清楚这些类固醇是否通过消除必要的宿主保护机制和/或通过失调寄生虫发育来促进过度感染。Ss生命周期阶段和Ss缺乏成功的方法。基因操纵。然而，通过最近的证明，目前存在新的可能性，即免疫缺陷 NOD.Cg -Prkdc scid ^Il2rg tm1Wjl /SzJ (NSG) 小鼠支持在糖皮质激素给药后可转化为致死性过度感染综合征的亚临床感染^。这与转录组学、转基因和基因失活策略的进步相结合，现在允许对Ss生物学进行严格的科学调查。我们建议将宿主免疫的体内操作和深度免疫分析策略与Ss转录组学的最新进展相结合，piggyBac转座子介导的转基因插入和 CRISPR/Cas-9 介导的基因失活将有助于对可靶向阻断Ss过度感染人类致死性的机制的新见解。