{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:23:26Z","timestamp":1790832206026,"version":"4.1.0"},"reference-count":69,"publisher":"Rockefeller University Press","issue":"3","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":224,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,2]]},"abstract":"<jats:p>The ability of Toxoplasma gondii to inject the rhoptry kinase ROP16 into host cells results in the activation of the transcription factors STAT3 and STAT6, but it is unclear how these events impact infection. Here, parasites that inject Cre-recombinase with rhoptry proteins were used to distinguish infected macrophages from those only injected with parasite proteins. Transcriptional profiling revealed that injection of rhoptry proteins alone was sufficient to induce an M2 phenotype that is dependent on STAT3 and STAT6, but only infected cells displayed reduced expression of genes associated with antimicrobial activity and protective immunity. In vivo, the absence of STAT3 or STAT6 improved parasite control, while the loss of ROP16 resulted in a marked reduction in parasite numbers and heightened parasite-specific T cell responses. Thus, ROP16 is a virulence factor that can act in cis and trans to promote M2 programs and which limits the magnitude of parasite-specific T cell responses.<\/jats:p>","DOI":"10.1084\/jem.20181757","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T14:36:19Z","timestamp":1579617379000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["The <i>Toxoplasma gondii<\/i> virulence factor ROP16 acts in cis and trans, and suppresses T cell responses"],"prefix":"10.1084","volume":"217","author":[{"given":"Longfei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China 1"},{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7160-9900","authenticated-orcid":false,"given":"David A.","family":"Christian","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-3159","authenticated-orcid":true,"given":"Joshua A.","family":"Kochanowsky","sequence":"additional","affiliation":[{"name":"Department of Neurology and Department of Immunobiology, BIO5 Institute, University of Arizona, Tucson, AZ 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-6070","authenticated-orcid":true,"given":"Anthony T.","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-6000","authenticated-orcid":true,"given":"Joseph T.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9348-2034","authenticated-orcid":true,"given":"Corbett","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7327-6794","authenticated-orcid":true,"given":"Jung","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphia, PA 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-691X","authenticated-orcid":true,"given":"Xiaoguang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Roos","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphia, PA 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Beiting","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-3233","authenticated-orcid":true,"given":"Anita A.","family":"Koshy","sequence":"additional","affiliation":[{"name":"Department of Neurology and Department of Immunobiology, BIO5 Institute, University of Arizona, Tucson, AZ 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-1428","authenticated-orcid":true,"given":"Christopher A.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"2023072716365806500_bib1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037349","article-title":"Lack of PPAR\u03b3 in myeloid cells confers resistance to Listeria monocytogenes infection","volume":"7","author":"Abdullah","year":"2012","journal-title":"PLoS One."},{"key":"2023072716365806500_bib2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001212","article-title":"Immune evasion by Yersinia enterocolitica: differential targeting of dendritic cell subpopulations in vivo","volume":"6","author":"Autenrieth","year":"2010","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002992","article-title":"The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18","volume":"8","author":"Behnke","year":"2012","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002200","article-title":"The orphan nuclear receptor TLX is an enhancer of STAT1-mediated transcription and immunity to Toxoplasma gondii","volume":"13","author":"Beiting","year":"2015","journal-title":"PLoS Biol."},{"key":"2023072716365806500_bib5","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1111\/cmi.12255","article-title":"Toxoplasma exports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression","volume":"16","author":"Bougdour","year":"2014","journal-title":"Cell. Microbiol."},{"key":"2023072716365806500_bib6","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"2023072716365806500_bib7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143593","article-title":"M2 polarization of human macrophages favors survival of the intracellular pathogen Chlamydia pneumoniae","volume":"10","author":"Buchacher","year":"2015","journal-title":"PLoS One."},{"key":"2023072716365806500_bib8","doi-asserted-by":"publisher","first-page":"3148","DOI":"10.4049\/jimmunol.174.6.3148","article-title":"IL-10-independent STAT3 activation by Toxoplasma gondii mediates suppression of IL-12 and TNF-\u03b1 in host macrophages","volume":"174","author":"Butcher","year":"2005","journal-title":"J. Immunol."},{"key":"2023072716365806500_bib9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002236","article-title":"Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control","volume":"7","author":"Butcher","year":"2011","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib10","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/B978-0-12-396481-6.00014-3","article-title":"Interactions between Toxoplasma effectors and host immune responses","volume-title":"Toxoplasma gondii.","author":"Butcher","year":"2014","edition":"Second edition"},{"key":"2023072716365806500_bib11","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/1521-4141(200102)31:2&lt;333::AID-IMMU333&gt;3.0.CO;2-X","article-title":"IL-4 and IL-13 regulate the induction of indoleamine 2,3-dioxygenase activity and the control of Toxoplasma gondii replication in human fibroblasts activated with IFN-\u03b3","volume":"31","author":"Chaves","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"2023072716365806500_bib12","doi-asserted-by":"publisher","first-page":"4056","DOI":"10.1128\/IAI.01643-14","article-title":"Use of transgenic parasites and host reporters to dissect events that promote interleukin-12 production during toxoplasmosis","volume":"82","author":"Christian","year":"2014","journal-title":"Infect. Immun."},{"key":"2023072716365806500_bib13","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.immuni.2016.06.013","article-title":"Continuous effector CD8(+) T cell production in a controlled persistent infection is sustained by a proliferative intermediate population","volume":"45","author":"Chu","year":"2016","journal-title":"Immunity."},{"key":"2023072716365806500_bib14","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.pt.2017.02.007","article-title":"The Toxoplasma parasitophorous vacuole: an evolving host-parasite frontier","volume":"33","author":"Clough","year":"2017","journal-title":"Trends Parasitol."},{"key":"2023072716365806500_bib15","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1128\/IAI.05974-11","article-title":"An inside job: hacking into Janus kinase\/signal transducer and activator of transcription signaling cascades by the intracellular protozoan Toxoplasma gondii.","volume":"80","author":"Denkers","year":"2012","journal-title":"Infect. Immun."},{"key":"2023072716365806500_bib16","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/bioinformatics\/btn224","article-title":"lumi: a pipeline for processing Illumina microarray","volume":"24","author":"Du","year":"2008","journal-title":"Bioinformatics."},{"key":"2023072716365806500_bib17","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.chom.2013.07.010","article-title":"Salmonella require the fatty acid regulator PPAR\u03b4 for the establishment of a metabolic environment essential for long-term persistence","volume":"14","author":"Eisele","year":"2013","journal-title":"Cell Host Microbe."},{"key":"2023072716365806500_bib18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030014","article-title":"ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii.","volume":"3","author":"El Hajj","year":"2007","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib19","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1038\/ni.1671","article-title":"Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens","volume":"9","author":"El Kasmi","year":"2008","journal-title":"Nat. Immunol."},{"key":"2023072716365806500_bib20","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.chom.2014.04.002","article-title":"The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice","volume":"15","author":"Etheridge","year":"2014","journal-title":"Cell Host Microbe."},{"key":"2023072716365806500_bib21","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1189\/jlb.2A1114-560R","article-title":"The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling","volume":"98","author":"Fleming","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"2023072716365806500_bib22","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00193-16","article-title":"The Toxoplasma gondii rhoptry kinome is essential for chronic infection","volume":"7","author":"Fox","year":"2016","journal-title":"MBio."},{"key":"2023072716365806500_bib23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006809","article-title":"STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control of infection with Mycobacterium tuberculosis.","volume":"14","author":"Gao","year":"2018","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib24","doi-asserted-by":"publisher","first-page":"902","DOI":"10.4049\/jimmunol.167.2.902","article-title":"IFN-\u03b3 overproduction and high level apoptosis are associated with high but not low virulence Toxoplasma gondii infection","volume":"167","author":"Gavrilescu","year":"2001","journal-title":"J. Immunol."},{"key":"2023072716365806500_bib25","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1084\/jem.20160340","article-title":"Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-\u03b3-mediated host defenses","volume":"213","author":"Gay","year":"2016","journal-title":"J. Exp. Med."},{"key":"2023072716365806500_bib26","doi-asserted-by":"crossref","first-page":"798","DOI":"10.4049\/jimmunol.157.2.798","article-title":"In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-\u03b3 and TNF-\u03b1","volume":"157","author":"Gazzinelli","year":"1996","journal-title":"J. Immunol."},{"key":"2023072716365806500_bib27","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.immuni.2010.05.007","article-title":"Alternative activation of macrophages: mechanism and functions","volume":"32","author":"Gordon","year":"2010","journal-title":"Immunity."},{"key":"2023072716365806500_bib28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023072716365806500_bib29","doi-asserted-by":"publisher","first-page":"3311","DOI":"10.1182\/blood-2010-02-271981","article-title":"Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2","volume":"116","author":"Huber","year":"2010","journal-title":"Blood."},{"key":"2023072716365806500_bib30","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with Bioconductor","volume":"12","author":"Huber","year":"2015","journal-title":"Nat. Methods."},{"key":"2023072716365806500_bib31","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/nrmicro2858","article-title":"Modulation of innate immunity by Toxoplasma gondii virulence effectors","volume":"10","author":"Hunter","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"2023072716365806500_bib32","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.chom.2011.04.015","article-title":"Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation","volume":"9","author":"Jensen","year":"2011","journal-title":"Cell Host Microbe."},{"key":"2023072716365806500_bib33","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1128\/IAI.01185-12","article-title":"Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15","volume":"81","author":"Jensen","year":"2013","journal-title":"Infect. Immun."},{"key":"2023072716365806500_bib34","doi-asserted-by":"publisher","first-page":"3894","DOI":"10.1128\/IAI.00024-09","article-title":"Kinetics and phenotype of vaccine-induced CD8+ T-cell responses to Toxoplasma gondii.","volume":"77","author":"Jordan","year":"2009","journal-title":"Infect. Immun."},{"key":"2023072716365806500_bib35","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nmeth.1438","article-title":"Toxoplasma secreting Cre recombinase for analysis of host-parasite interactions","volume":"7","author":"Koshy","year":"2010","journal-title":"Nat. Methods."},{"key":"2023072716365806500_bib36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002825","article-title":"Toxoplasma co-opts host cells it does not invade","volume":"8","author":"Koshy","year":"2012","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib37","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1084\/jem.20171389","article-title":"Mannose receptor high, M2 dermal macrophages mediate nonhealing Leishmania major infection in a Th1 immune environment","volume":"215","author":"Lee","year":"2018","journal-title":"J. Exp. Med."},{"key":"2023072716365806500_bib38","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nat. Neurosci."},{"key":"2023072716365806500_bib39","doi-asserted-by":"publisher","first-page":"5593","DOI":"10.4049\/jimmunol.1103038","article-title":"Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPAR\u03b3 and TR4 for survival","volume":"188","author":"Mahajan","year":"2012","journal-title":"J. Immunol."},{"key":"2023072716365806500_bib40","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1097\/QCO.0b013e328344b73e","article-title":"Macrophage polarization and bacterial infections","volume":"24","author":"M\u00e8ge","year":"2011","journal-title":"Curr. Opin. Infect. Dis."},{"key":"2023072716365806500_bib41","doi-asserted-by":"publisher","first-page":"4883","DOI":"10.1128\/IAI.01288-07","article-title":"The \u03b3 interferon (IFN-\u03b3)-inducible GTP-binding protein IGTP is necessary for toxoplasma vacuolar disruption and induces parasite egression in IFN-\u03b3-stimulated astrocytes","volume":"76","author":"Melzer","year":"2008","journal-title":"Infect. Immun."},{"key":"2023072716365806500_bib42","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/0378-1119(95)00548-K","article-title":"Stable DNA transformation of Toxoplasma gondii using phleomycin selection","volume":"165","author":"Messina","year":"1995","journal-title":"Gene."},{"key":"2023072716365806500_bib43","doi-asserted-by":"publisher","first-page":"4574","DOI":"10.4049\/jimmunol.167.8.4574","article-title":"Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines","volume":"167","author":"Mordue","year":"2001","journal-title":"J. Immunol."},{"key":"2023072716365806500_bib44","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1093\/intimm\/dxg108","article-title":"TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection","volume":"15","author":"Mun","year":"2003","journal-title":"Int. Immunol."},{"key":"2023072716365806500_bib45","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.chom.2011.05.010","article-title":"Macrophages as a battleground for toxoplasma pathogenesis","volume":"9","author":"Murray","year":"2011","journal-title":"Cell Host Microbe."},{"key":"2023072716365806500_bib46","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1128\/iai.65.5.1675-1682.1997","article-title":"Role of interleukin-10 in regulation of T-cell-dependent and T-cell-independent mechanisms of resistance to Toxoplasma gondii.","volume":"65","author":"Neyer","year":"1997","journal-title":"Infect. Immun."},{"key":"2023072716365806500_bib47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002784","article-title":"The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-\u03b3 response","volume":"8","author":"Niedelman","year":"2012","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib48","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.chom.2016.06.006","article-title":"Toxoplasma effector recruits the Mi-2\/NuRD complex to repress STAT1 transcription and block IFN-\u03b3-dependent gene expression","volume":"20","author":"Olias","year":"2016","journal-title":"Cell Host Microbe."},{"key":"2023072716365806500_bib49","doi-asserted-by":"publisher","first-page":"28731","DOI":"10.1074\/jbc.M110.112359","article-title":"Toxoplasma rhoptry protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6","volume":"285","author":"Ong","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2023072716365806500_bib50","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1126\/science.1256942","article-title":"Coinfection. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation","volume":"345","author":"Osborne","year":"2014","journal-title":"Science."},{"key":"2023072716365806500_bib51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004981","article-title":"Illuminating targets of bacterial secretion","volume":"11","author":"Pechous","year":"2015","journal-title":"PLoS Pathog."},{"key":"2023072716365806500_bib52","doi-asserted-by":"publisher","first-page":"9954","DOI":"10.1073\/pnas.1707098114","article-title":"Injection of T3SS effectors not resulting in invasion is the main targeting mechanism of Shigella toward human lymphocytes","volume":"114","author":"Pinaud","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072716365806500_bib53","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.immuni.2014.10.015","article-title":"The macrophage paradox","volume":"41","author":"Price","year":"2014","journal-title":"Immunity."},{"key":"2023072716365806500_bib54","doi-asserted-by":"publisher","first-page":"929","DOI":"10.4049\/jimmunol.1000866","article-title":"Mycobacterium tuberculosis activates human macrophage peroxisome proliferator-activated receptor \u03b3 linking mannose receptor recognition to regulation of immune responses","volume":"185","author":"Rajaram","year":"2010","journal-title":"J. Immunol."},{"key":"2023072716365806500_bib55","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/mt.2012.168","article-title":"IFN-\u03b3-induced iNOS expression in mouse regulatory macrophages prolongs allograft survival in fully immunocompetent recipients","volume":"21","author":"Riquelme","year":"2013","journal-title":"Mol. Ther."},{"key":"2023072716365806500_bib56","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2023072716365806500_bib57","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.pt.2005.08.001","article-title":"Differences among the three major strains of Toxoplasma gondii and their specific interactions with the infected host","volume":"21","author":"Saeij","year":"2005","journal-title":"Trends Parasitol."},{"key":"2023072716365806500_bib58","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1126\/science.1133690","article-title":"Polymorphic secreted kinases are key virulence factors in toxoplasmosis","volume":"314","author":"Saeij","year":"2006","journal-title":"Science."},{"key":"2023072716365806500_bib59","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nature05395","article-title":"Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue","volume":"445","author":"Saeij","year":"2007","journal-title":"Nature."},{"key":"2023072716365806500_bib60","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/j.1600-065X.2010.00990.x","article-title":"Invasion and intracellular survival by protozoan parasites","volume":"240","author":"Sibley","year":"2011","journal-title":"Immunol. Rev."},{"key":"2023072716365806500_bib61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000576","article-title":"Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent Toxoplasma gondii.","volume":"8","author":"Steinfeldt","year":"2010","journal-title":"PLoS Biol."},{"key":"2023072716365806500_bib62","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072716365806500_bib63","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/ni.3023","article-title":"Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage","volume":"15","author":"Sutherland","year":"2014","journal-title":"Nat. Immunol."},{"key":"2023072716365806500_bib64","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1681\/ASN.2013060675","article-title":"Colony-stimulating factor-1 signaling suppresses renal crystal formation","volume":"25","author":"Taguchi","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"2023072716365806500_bib65","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1126\/science.1133643","article-title":"A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii.","volume":"314","author":"Taylor","year":"2006","journal-title":"Science."},{"issue":"10","key":"2023072716365806500_bib66","doi-asserted-by":"publisher","first-page":"e1007856","DOI":"10.1371\/journal.ppat.1007856","article-title":"The ROP16III-dependent early immune response determines the subacute CNS immune response and type III Toxoplasma gondii survival","volume":"15","author":"Tuladhar","year":"2019","journal-title":"PLoS Pathog"},{"key":"2023072716365806500_bib67","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.chom.2013.07.009","article-title":"PPAR\u03b3-mediated increase in glucose availability sustains chronic Brucella abortus infection in alternatively activated macrophages","volume":"14","author":"Xavier","year":"2013","journal-title":"Cell Host Microbe."},{"key":"2023072716365806500_bib68","doi-asserted-by":"publisher","first-page":"2747","DOI":"10.1084\/jem.20091703","article-title":"A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3","volume":"206","author":"Yamamoto","year":"2009","journal-title":"J. Exp. Med."},{"key":"2023072716365806500_bib69","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1084\/jem.20050324","article-title":"Interleukin (IL)-4 inhibits IL-10 to promote IL-12 production by dendritic cells","volume":"201","author":"Yao","year":"2005","journal-title":"J. Exp. Med."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20181757\/1817085\/jem_20181757.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20181757\/1817085\/jem_20181757.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T16:38:14Z","timestamp":1690475894000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/217\/3\/e20181757\/133618\/The-Toxoplasma-gondii-virulence-factor-ROP16-acts"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,20]]},"references-count":69,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3,2]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20181757","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,20]]},"article-number":"e20181757"}}