{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:47:59Z","timestamp":1792100879653,"version":"4.4.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The apicomplexan parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    infects various cell types in avian and mammalian hosts including humans. Infection of immunocompetent hosts is mostly asymptomatic or benign, but leads to development of largely dormant bradyzoites that persist predominantly within neurons and muscle cells. Here we have analyzed the impact of the host cell type on the co-transcriptomes of host and parasite using high-throughput RNA sequencing. Murine cortical neurons and astrocytes, skeletal muscle cells (SkMCs) and fibroblasts differed by more than 16,200 differentially expressed genes (DEGs) before and after infection with\n                    <jats:italic>T. gondii<\/jats:italic>\n                    . However, only a few hundred of them were regulated by infection and these largely diverged in neurons, SkMCs, astrocytes and fibroblasts indicating host cell type-specific transcriptional responses after infection. The heterogeneous transcriptomes of host cells before and during infection coincided with ~5,400 DEGs in\n                    <jats:italic>T. gondii<\/jats:italic>\n                    residing in different cell types. Finally, we identified gene clusters in both\n                    <jats:italic>T. gondii<\/jats:italic>\n                    and its host, which correlated with the predominant parasite persistence in neurons or SkMCs as compared to astrocytes or fibroblasts. Thus, heterogeneous expression profiles of different host cell types and the parasites\u2019 ability to adapting to them may govern the parasite-host cell interaction during toxoplasmosis.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-07838-w","type":"journal-article","created":{"date-parts":[[2017,7,28]],"date-time":"2017-07-28T10:53:09Z","timestamp":1501239189000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host-parasite interactions"],"prefix":"10.1038","volume":"7","author":[{"given":"Izabela J.","family":"Swierzy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"H\u00e4ndel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kaever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Scharfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Schl\u00fcter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-6356","authenticated-orcid":false,"given":"Carsten G. K.","family":"L\u00fcder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,3]]},"reference":[{"key":"7838_CR1","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.4315\/0362-028X.JFP-11-417","volume":"75","author":"S Hoffmann","year":"2012","unstructured":"Hoffmann, S., Batz, M. B. & Morris, J. G. Jr. Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens. J Food Prot \n                           75, 1292\u20131302, doi:10.4315\/0362-028X.JFP-11-417 (2012).","journal-title":"J Food Prot"},{"key":"7838_CR2","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","volume":"363","author":"JG Montoya","year":"2004","unstructured":"Montoya, J. G. & Liesenfeld, O. Toxoplasmosis. Lancet \n                           363, 1965\u20131976 (2004).","journal-title":"Lancet"},{"key":"7838_CR3","doi-asserted-by":"crossref","unstructured":"Tenter, A. M., Heckeroth, A. R. & Weiss, L. M. Toxoplasma gondii: from animals to humans. Int J Parasitol \n                           30, 1217\u20131258, doi:S0020-7519(00)00124-7 [pii] (2000).","DOI":"10.1016\/S0020-7519(00)00124-7"},{"key":"7838_CR4","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1590\/S0074-02762009000200009","volume":"104","author":"JC Boothroyd","year":"2009","unstructured":"Boothroyd, J. C. Expansion of host range as a driving force in the evolution of Toxoplasma. Mem Inst Oswaldo Cruz \n                           104, 179\u2013184 (2009).","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"7838_CR5","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/S0092-8674(00)81071-5","volume":"84","author":"JM Dobrowolski","year":"1996","unstructured":"Dobrowolski, J. M. & Sibley, L. D. Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. Cell \n                           84, 933\u2013939 (1996). doi:S0092-8674(00)81071-5 [pii].","journal-title":"Cell"},{"key":"7838_CR6","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.chom.2010.09.002","volume":"8","author":"K Frenal","year":"2010","unstructured":"Frenal, K. et al. Functional dissection of the apicomplexan glideosome molecular architecture. Cell Host Microbe \n                           8, 343\u2013357, doi:10.1016\/j.chom.2010.09.002 (2010).","journal-title":"Cell Host Microbe"},{"key":"7838_CR7","doi-asserted-by":"publisher","first-page":"4822","DOI":"10.1128\/IAI.68.8.4822-4826.2000","volume":"68","author":"JY Channon","year":"2000","unstructured":"Channon, J. Y., Seguin, R. M. & Kasper, L. H. Differential infectivity and division of Toxoplasma gondii in human peripheral blood leukocytes. Infect Immun \n                           68, 4822\u20134826 (2000).","journal-title":"Infect Immun"},{"key":"7838_CR8","doi-asserted-by":"publisher","first-page":"D391","DOI":"10.2741\/A521","volume":"5","author":"LM Weiss","year":"2000","unstructured":"Weiss, L. M. & Kim, K. The development and biology of bradyzoites of Toxoplasma gondii. Frontiers in bioscience: a journal and virtual library \n                           5, D391\u2013405 (2000).","journal-title":"Frontiers in bioscience: a journal and virtual library"},{"key":"7838_CR9","doi-asserted-by":"crossref","unstructured":"Radke, J. R., Guerini, M. N., Jerome, M. & White, M. W. A change in the premitotic period of the cell cycle is associated with bradyzoite differentiation in Toxoplasma gondii. 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Mol Biosyst \n                           4, 824\u2013834, doi:10.1039\/b800520f (2008).","journal-title":"Mol Biosyst"},{"key":"7838_CR14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1006\/expr.1999.4421","volume":"93","author":"CG L\u00fcder","year":"1999","unstructured":"L\u00fcder, C. G., Giraldo-Velasquez, M., Sendtner, M. & Gross, U. Toxoplasma gondii in primary rat CNS cells: differential contribution of neurons, astrocytes, and microglial cells for the intracerebral development and stage differentiation. Exp Parasitol \n                           93, 23\u201332, doi:10.1006\/expr.1999.4421 (1999).","journal-title":"Exp Parasitol"},{"key":"7838_CR15","doi-asserted-by":"publisher","unstructured":"Ferreira-da-Silva Mda, F., Takacs, A. C., Barbosa, H. S., Gross, U. & Luder, C. G. Primary skeletal muscle cells trigger spontaneous Toxoplasma gondii tachyzoite-to-bradyzoite conversion at higher rates than fibroblasts. Int J Med Microbiol \n                           299, 381\u2013388, doi:10.1016\/j.ijmm.2008.10.002 (2009).","DOI":"10.1016\/j.ijmm.2008.10.002"},{"key":"7838_CR16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/cmi.12342","volume":"17","author":"IJ Swierzy","year":"2015","unstructured":"Swierzy, I. J. & Luder, C. G. Withdrawal of skeletal muscle cells from cell cycle progression triggers differentiation of Toxoplasma gondii towards the bradyzoite stage. Cell Microbiol \n                           17, 2\u201317, doi:10.1111\/cmi.12342 (2015).","journal-title":"Cell Microbiol"},{"key":"7838_CR17","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1471-2105-10-92","volume":"10","author":"A Kaever","year":"2009","unstructured":"Kaever, A. et al. MarVis: a tool for clustering and visualization of metabolic biomarkers. BMC Bioinformatics \n                           10, 92, doi:10.1186\/1471-2105-10-92 (2009).","journal-title":"BMC Bioinformatics"},{"key":"7838_CR18","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1007\/s11306-014-0734-y","volume":"11","author":"A Kaever","year":"2015","unstructured":"Kaever, A. et al. MarVis-Pathway: integrative and exploratory pathway analysis of non-targeted metabolomics data. Metabolomics \n                           11, 764\u2013777, doi:10.1007\/s11306-014-0734-y (2015).","journal-title":"Metabolomics"},{"key":"7838_CR19","doi-asserted-by":"publisher","first-page":"16312","DOI":"10.1073\/pnas.1205589109","volume":"109","author":"DA Mahamed","year":"2012","unstructured":"Mahamed, D. A., Mills, J. H., Egan, C. E., Denkers, E. Y. & Bynoe, M. S. CD73-generated adenosine facilitates Toxoplasma gondii differentiation to long-lived tissue cysts in the central nervous system. Proc Natl Acad Sci USA \n                           109, 16312\u201316317, doi:10.1073\/pnas.1205589109 (2012).","journal-title":"Proc Natl Acad Sci USA"},{"key":"7838_CR20","doi-asserted-by":"publisher","first-page":"24223","DOI":"10.1074\/jbc.M100951200","volume":"276","author":"IJ Blader","year":"2001","unstructured":"Blader, I. J., Manger, I. D. & Boothroyd, J. C. Microarray analysis reveals previously unknown changes in Toxoplasma gondii-infected human cells. J Biol Chem \n                           276, 24223\u201324231, doi:10.1074\/jbc.M100951200 (2001).","journal-title":"J Biol Chem"},{"key":"7838_CR21","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1111\/j.1365-2958.1995.tb02344.x","volume":"16","author":"W Bohne","year":"1995","unstructured":"Bohne, W., Gross, U., Ferguson, D. J. & Heesemann, J. Cloning and characterization of a bradyzoite-specifically expressed gene (hsp30\/bag1) of Toxoplasma gondii, related to genes encoding small heat-shock proteins of plants. Mol Microbiol \n                           16, 1221\u20131230 (1995).","journal-title":"Mol Microbiol"},{"key":"7838_CR22","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/mmi.12121","volume":"87","author":"R Walker","year":"2013","unstructured":"Walker, R. et al. The Toxoplasma nuclear factor TgAP2XI-4 controls bradyzoite gene expression and cyst formation. Mol Microbiol \n                           87, 641\u2013655, doi:10.1111\/mmi.12121 (2013).","journal-title":"Mol Microbiol"},{"key":"7838_CR23","doi-asserted-by":"publisher","first-page":"6871","DOI":"10.1073\/pnas.1300059110","volume":"110","author":"JB Radke","year":"2013","unstructured":"Radke, J. B. et al. ApiAP2 transcription factor restricts development of the Toxoplasma tissue cyst. Proc Natl Acad Sci USA \n                           110, 6871\u20136876, doi:10.1073\/pnas.1300059110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"7838_CR24","doi-asserted-by":"publisher","first-page":"e1000784","DOI":"10.1371\/journal.ppat.1000784","volume":"6","author":"C Flueck","year":"2010","unstructured":"Flueck, C. et al. A major role for the Plasmodium falciparum ApiAP2 protein PfSIP2 in chromosome end biology. PLoS Pathog \n                           6, e1000784, doi:10.1371\/journal.ppat.1000784 (2010).","journal-title":"PLoS Pathog"},{"key":"7838_CR25","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.exppara.2011.01.015","volume":"127","author":"A Ueno","year":"2011","unstructured":"Ueno, A. et al. Toxoplasma gondii: a bradyzoite-specific DnaK-tetratricopeptide repeat (DnaK-TPR) protein interacts with p23 co-chaperone protein. Exp Parasitol \n                           127, 795\u2013803, doi:10.1016\/j.exppara.2011.01.015 (2011).","journal-title":"Exp Parasitol"},{"key":"7838_CR26","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1186\/1471-2164-15-806","volume":"15","author":"KJ Pittman","year":"2014","unstructured":"Pittman, K. J., Aliota, M. T. & Knoll, L. J. Dual transcriptional profiling of mice and Toxoplasma gondii during acute and chronic infection. BMC Genomics \n                           15, 806, doi:10.1186\/1471-2164-15-806 (2014).","journal-title":"BMC Genomics"},{"key":"7838_CR27","doi-asserted-by":"crossref","unstructured":"Knoll, L. J., Tomita, T., Weiss, L. M. in Toxoplasma gondii. The Model Apicomplexan: Perspectives and Methods (ed L. M. Weiss, Kim, K.) Ch. 15, 521\u2013549 (Academic Press, 2014).","DOI":"10.1016\/B978-0-12-396481-6.00015-5"},{"key":"7838_CR28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1128\/CMR.11.2.267","volume":"11","author":"JP Dubey","year":"1998","unstructured":"Dubey, J. P., Lindsay, D. S. & Speer, C. A. Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev \n                           11, 267\u2013299 (1998).","journal-title":"Clin Microbiol Rev"},{"key":"7838_CR29","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1073\/pnas.91.2.509","volume":"91","author":"JC Schwab","year":"1994","unstructured":"Schwab, J. C., Beckers, C. J. & Joiner, K. A. The parasitophorous vacuole membrane surrounding intracellular Toxoplasma gondii functions as a molecular sieve. 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Blood \n                           102, 672\u2013681, doi:10.1182\/blood-2002-10-3232 (2003).","journal-title":"Blood"},{"key":"7838_CR34","doi-asserted-by":"crossref","unstructured":"Ferreira-da-Silva Mda, F. et al. Spontaneous stage differentiation of mouse-virulent Toxoplasma gondii RH parasites in skeletal muscle cells: an ultrastructural evaluation. Mem Inst Oswaldo Cruz \n                           104, 196\u2013200, doi:S0074-02762009000200012 [pii] (2009).","DOI":"10.1590\/S0074-02762009000200012"},{"key":"7838_CR35","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1371\/journal.ppat.0020105","volume":"2","author":"JR Radke","year":"2006","unstructured":"Radke, J. R. et al. Changes in the expression of human cell division autoantigen-1 influence Toxoplasma gondii growth and development. 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