Toxoplasma and Eimeria co-opt the host cFos expression for intracellular development in mammalian cells

Bingjian Ren; Manuela Schmid; Mattea Scheiner; Hans-Joachim Mollenkopf; Richard Lucius; Emanuel Heitlinger; Nishith Gupta

doi:10.1016/j.csbj.2020.12.045

Toxoplasma and Eimeria co-opt the host cFos expression for intracellular development in mammalian cells

Comput Struct Biotechnol J. 2021 Jan 6:19:719-731. doi: 10.1016/j.csbj.2020.12.045. eCollection 2021.

Authors

Bingjian Ren¹, Manuela Schmid¹, Mattea Scheiner¹, Hans-Joachim Mollenkopf², Richard Lucius¹, Emanuel Heitlinger^{1

3}, Nishith Gupta^{1

4}

Affiliations

¹ Department of Molecular Parasitology, Institute of Biology, Humboldt University, Berlin, Germany.
² Microarray and Genomics Core Facility, Max-Planck Institute for Infection Biology, Berlin, Germany.
³ Research Group Ecology and Evolution of Parasite Host Interactions, Leibniz Institute for Zoo and Wildlife Research, Berlin, Germany.
⁴ Department of Biological Sciences, Birla Institute of Technology and Science Pilani (BITS-P), Hyderabad, India.

Abstract

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.

Keywords: Coccidia; Eimeria falciformis; Gene Expression Analysis; Microarrays; Parasite-Host Interaction; Toxoplasma gondii; Transcriptomics.