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 Toxoplasma gondii and Eimeria falciformis, 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 T. gondii and E. falciformis, 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.

细胞内病原体能否成功进行无性繁殖取决于其利用宿主资源并破坏抗菌素防御能力的潜力。在这项工作中，我们部署了两种普遍存在的哺乳动物细胞的apicomplexan寄生虫，即弓形虫和恶性艾美球虫。，以确定潜在的宿主感染因素。任一种寄生虫感染后，年轻成年小鼠结肠（YAMC）上皮细胞的表达分析均显示出几种不同转录本的调控，表明这两种病原体以定制方式编程其细胞内壁ches。相反，与相应的YAMC上皮细胞相比，寄生的小鼠胚胎成纤维细胞（MEF）显示出不同的转录组，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。在刚被弓形虫和恶性大肠杆菌改变的几个宿主转录物中，我们确定了cFos，一种主要的转录因子，在整个感染过程中一直被诱导。实际上，在缺乏cFos表达的MEF宿主细胞中，两种寄生虫的无性生长都受到了严重损害。最后但并非最不重要的一点是，我们对感染的MEF（亲代和cFos ^-/-突变体）和YAMC上皮细胞的差异转录组学揭示了一个以cFos为中心的网络，潜在的信号级联以及核苷酸和离子结合蛋白的种类。推测其协同作用以使哺乳动物细胞适应，从而促进寄生虫的发育。