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Here, using genetic crosses between type II and type III<jats:named-content content-type=\"genus-species\">Toxoplasma<\/jats:named-content>strains and quantitative trait locus (QTL) mapping of the changes they induce in macrophage gene expression, we identify a novel dense granule protein, GRA25. Encoded on chromosome IX, GRA25 is a phosphoprotein that is secreted outside the parasites and is found within the parasitophorous vacuole.<jats:italic>In vitro<\/jats:italic>experiments with a type II \u0394<jats:italic>gra25<\/jats:italic>strain showed that macrophages infected with this strain secrete lower levels of CCL2 and CXCL1 than those infected with the wild-type or complemented control parasites.<jats:italic>In vivo<\/jats:italic>experiments showed that mice infected with a type II \u0394<jats:italic>gra25<\/jats:italic>strain are able to survive an otherwise lethal dose of<jats:named-content content-type=\"genus-species\">Toxoplasma<\/jats:named-content>tachyzoites and that complementation of the mutant with an ectopic copy of<jats:italic>GRA25<\/jats:italic>largely rescues this phenotype. Interestingly, the type II and type III versions of GRA25 differ in endogenous expression levels; however, both are able to promote parasite expansion<jats:italic>in vivo<\/jats:italic>when expressed in a type II \u0394<jats:italic>gra25<\/jats:italic>strain. These data establish GRA25 as a novel virulence factor and immune modulator.<\/jats:p>","DOI":"10.1128\/iai.01339-13","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T06:06:51Z","timestamp":1396937211000},"page":"2595-2605","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":72,"title":["GRA25 Is a Novel Virulence Factor of Toxoplasma gondii and Influences the Host Immune Response"],"prefix":"10.1128","volume":"82","author":[{"given":"Anjali J.","family":"Shastri","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole D.","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa B.","family":"Lodoen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Boothroyd","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.4049\/jimmunol.153.6.2533","article-title":"Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii","volume":"153","author":"Gazzinelli RT","year":"1994","unstructured":"GazzinelliRTWysockaMHayashiSDenkersEYHienySCasparPTrinchieriGSherA. 1994. 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