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The predicted bZIP transcription factor ZIP-1 promotes resistance to intracellular infection in Caenorhabditis elegans
bioRxiv - Immunology Pub Date : 2021-09-13 , DOI: 10.1101/2021.06.17.448850
Vladimir Lažetić , Fengting Wu , Lianne B. Cohen , Kirthi C. Reddy , Ya-Ting Chang , Spencer S. Gang , Gira Bhabha , Emily R. Troemel

Defense against intracellular infection has been extensively studied in vertebrate hosts, but less is known about invertebrate hosts. For example, almost nothing is known about the transcription factors that induce defense against intracellular intestinal infection in the model nematode Caenorhabditis elegans. Two types of intracellular pathogens that naturally infect the C. elegans intestine are the Orsay virus, which is a positive-sense RNA virus, and microsporidia, which are fungal pathogens. Surprisingly, these molecularly distinct pathogens induce a common host transcriptional response called the Intracellular Pathogen Response (IPR). Here we describe zip-1 as an IPR regulator that functions downstream of all known IPR activating and regulatory pathways. zip-1 encodes a putative bZIP transcription factor of previously unknown function, and we show how zip-1 controls induction of a subset of genes upon IPR activation. ZIP-1 protein is expressed in the nuclei of intestinal cells, and is required in the intestine to upregulate IPR gene expression. Importantly, zip-1 promotes resistance to infection by the Orsay virus and by microsporidia in intestinal cells. Altogether, our results indicate that zip-1 represents a central hub for all triggers of the IPR, and that this transcription factor plays a protective role against intracellular pathogen infection in C. elegans.

中文翻译:

预测的 bZIP 转录因子 ZIP-1 促进秀丽隐杆线虫对细胞内感染的抵抗力

在脊椎动物宿主中对细胞内感染的防御进行了广泛的研究,但对无脊椎动物宿主知之甚少。例如,在模型线虫秀丽隐杆线虫中诱导防御细胞内肠道感染的转录因子几乎一无所知自然感染秀丽隐杆线虫肠道的两种细胞内病原体是奥赛病毒(一种正链 RNA 病毒)和微孢子虫(真菌病原体)。令人惊讶的是,这些分子上不同的病原体诱导了一种常见的宿主转录反应,称为细胞内病原体反应 (IPR)。这里我们描述zip-1作为知识产权监管者,在所有已知知识产权激活和监管途径的下游发挥作用。zip-1编码一个先前未知功能的假定 bZIP 转录因子,我们展示了zip-1如何控制 IPR 激活后基因子集的诱导。ZIP-1 蛋白在肠细胞的细胞核中表达,需要在肠内上调 IPR 基因表达。重要的是,zip-1促进对奥赛病毒和肠道细胞中微孢子虫感染的抵抗力。总而言之,我们的结果表明zip-1代表了所有 IPR 触发因素的中心枢纽,并且该转录因子对线虫中的细胞内病原体感染起着保护作用.
更新日期:2021-09-15
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