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从病原体识别到多代抗性,对秀丽隐杆线虫先天免疫反应的机体理解。

An organismal understanding of C. elegans innate immune responses, from pathogen recognition to multigenerational resistance.

机构信息

Department of Biology San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA.

Department of Biology San Diego State University, 5500 Campanile Dr., San Diego, CA 92182, USA.

出版信息

Semin Cell Dev Biol. 2024 Feb 15;154(Pt A):77-84. doi: 10.1016/j.semcdb.2023.03.005. Epub 2023 Mar 23.

Abstract

The nematode Caenorhabditis elegans has been a model for studying infection since the early 2000s and many major discoveries have been made regarding its innate immune responses. C. elegans has been found to utilize some key conserved aspects of immune responses and signaling, but new interesting features of innate immunity have also been discovered in the organism that might have broader implications in higher eukaryotes such as mammals. Some of the distinctive features of C. elegans innate immunity involve the mechanisms this bacterivore uses to detect infection and mount specific immune responses to different pathogens, despite lacking putative orthologs of many important innate immune components, including cellular immunity, the inflammasome, complement, or melanization. Even when orthologs of known immune factors exist, there appears to be an absence of canonical functions, most notably the lack of pattern recognition by its sole Toll-like receptor. Instead, recent research suggests that C. elegans senses infection by specific pathogens through contextual information, including unique products produced by the pathogen or infection-induced disruption of host physiology, similar to the proposed detection of patterns of pathogenesis in mammalian systems. Interestingly, C. elegans can also transfer information of past infection to their progeny, providing robust protection for their offspring in face of persisting pathogens, in part through the RNAi pathway as well as potential new mechanisms that remain to be elucidated. Altogether, some of these strategies employed by C. elegans share key conceptual features with vertebrate adaptive immunity, as the animal can differentiate specific microbial features, as well as propagate a form of immune memory to their offspring.

摘要

秀丽隐杆线虫自 21 世纪初以来一直是研究感染的模式生物,在其先天免疫反应方面取得了许多重大发现。已经发现秀丽隐杆线虫利用了免疫反应和信号转导的一些关键保守方面,但在该生物中也发现了先天免疫的新有趣特征,这些特征可能在哺乳动物等高等真核生物中具有更广泛的意义。秀丽隐杆线虫先天免疫的一些独特特征涉及到这种食细菌生物用来检测感染并针对不同病原体产生特定免疫反应的机制,尽管它缺乏许多重要先天免疫成分的假定同源物,包括细胞免疫、炎症小体、补体或黑化。即使存在已知免疫因子的同源物,似乎也缺乏典型的功能,最显著的是缺乏其唯一的 Toll 样受体的模式识别。相反,最近的研究表明,秀丽隐杆线虫通过特定病原体的上下文信息来感知感染,包括病原体产生的独特产物或感染诱导的宿主生理学破坏,类似于在哺乳动物系统中提出的对发病模式的检测。有趣的是,秀丽隐杆线虫还可以将过去感染的信息传递给它们的后代,为它们的后代提供对持续存在的病原体的强大保护,部分是通过 RNAi 途径以及可能仍有待阐明的潜在新机制。总的来说,秀丽隐杆线虫采用的一些策略与脊椎动物适应性免疫具有关键的概念特征,因为动物可以区分特定的微生物特征,并将一种免疫记忆形式传递给它们的后代。

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