title: An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells.
abstract: Toxoplasmosis is a zoonotic infection affecting approximately 30% of the world's human population. After sexual reproduction in the definitive feline host, Toxoplasma oocysts, each containing 8 sporozoites, are shed into the environment where they can go on to infect humans and other warm-blooded intermediate hosts. Here, we use an in vitro model to assess host transcriptomic changes that occur in the earliest stages of such infections. We show that infection of rat intestinal epithelial cells with mature sporozoites primarily results in higher expression of genes associated with Tumor Necrosis Factor alpha (TNFα) signaling via NF-κB. Furthermore, we find that, consistent with their biology, these mature, invaded sporozoites display a transcriptome intermediate between the previously reported day 10 oocysts and that of their tachyzoite counterparts. Thus, this study uncovers novel host and pathogen factors that may be critical for the establishment of a successful intracellular niche following sporozoite-initiated infection.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Pascale S
authors.identifier: http://orcid.org/0000-0002-8186-3515
authors.initials: PS
authors.lastname: Guiton
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Sagawa
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Fritz
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism; D051381:Rats; D034101:Sporozoites / Q000378:metabolism*; D014122:Toxoplasma / Q000235:genetics*; D014123:Toxoplasmosis / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha