Ren Bingjian, Schmid Manuela, Scheiner Mattea, Mollenkopf Hans-Joachim, Lucius Richard, Heitlinger Emanuel, Gupta Nishith
Department of Molecular Parasitology, Institute of Biology, Humboldt University, Berlin, Germany.
Microarray and Genomics Core Facility, Max-Planck Institute for Infection Biology, Berlin, Germany.
Comput Struct Biotechnol J. 2021 Jan 6;19:719-731. doi: 10.1016/j.csbj.2020.12.045. eCollection 2021.
Successful asexual reproduction of intracellular pathogens depends on their potential to exploit host resources and subvert antimicrobial defense. In this work, we deployed two prevalent apicomplexan parasites of mammalian cells, namely and , to identify potential host determinants of infection. Expression analyses of the young adult mouse colonic (YAMC) epithelial cells upon infection by either parasite showed regulation of several distinct transcripts, indicating that these two pathogens program their intracellular niches in a tailored manner. Conversely, parasitized mouse embryonic fibroblasts (MEFs) displayed a divergent transcriptome compared to corresponding YAMC epithelial cells, suggesting that individual host cells mount a fairly discrete response when encountering a particular pathogen. Among several host transcripts similarly altered by and , we identified cFos, a master transcription factor, that was consistently induced throughout the infection. Indeed, asexual growth of both parasites was strongly impaired in MEF host cells lacking cFos expression. Last but not the least, our differential transcriptomics of the infected MEFs (parental and cFos mutant) and YAMC epithelial cells disclosed a cFos-centered network, underlying signal cascades, as well as a repertoire of nucleotides- and ion-binding proteins, which presumably act in consort to acclimatize the mammalian cell and thereby facilitate the parasite development.
细胞内病原体的成功无性繁殖取决于它们利用宿主资源和破坏抗菌防御的能力。在这项研究中，我们利用两种常见的感染哺乳动物细胞的顶复门寄生虫，即[寄生虫名称1]和[寄生虫名称2]，来确定感染的潜在宿主决定因素。用这两种寄生虫感染年轻成年小鼠结肠（YAMC）上皮细胞后的表达分析显示，有几种不同的转录本受到调控，这表明这两种病原体以一种定制的方式规划它们在细胞内的生态位。相反，与相应的YAMC上皮细胞相比，被寄生的小鼠胚胎成纤维细胞（MEF）表现出不同的转录组，这表明单个宿主细胞在遇到特定病原体时会产生相当离散的反应。在[寄生虫名称1]和[寄生虫名称2]类似改变的几种宿主转录本中，我们鉴定出一种主要转录因子cFos，它在整个感染过程中持续被诱导。事实上，在缺乏cFos表达的MEF宿主细胞中，这两种寄生虫的无性生长都受到严重损害。最后但同样重要的是，我们对受感染的MEF（亲本和cFos突变体）和YAMC上皮细胞进行的差异转录组学分析揭示了一个以cFos为中心的网络、潜在的信号级联以及一系列核苷酸和离子结合蛋白，它们可能协同作用以使哺乳动物细胞适应环境，从而促进寄生虫的发育。
