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Although non-cystogenic strains are considered the most virulent, there are also marked genetic and virulence differences among these strains. Excretory-secretory antigens (ESAs) of <jats:italic>T. gondii<\/jats:italic> are critical for the invasion process and the immune response of the host. To better understand the differences in virulence between non-cystogenic <jats:italic>T. gondii<\/jats:italic> isolates, we studied ESAs of the RH strain (Type I), and the very prevalent in China, but less virulent TgCtwh3 strain (Chinese 1). ESAs of RH and TgCtwh3 triggered different levels of TNF-\u03b1 production and macrophage M1 polarization. Using iTRAQ analysis, 27 differentially expressed proteins originating from secretory organelles and surface were quantified. Of these proteins, 11 microneme-associated proteins (MICs), 6 rhoptry proteins, 2 dense granule proteins and 5 surface proteins were more abundant in RH than in TgCtwh3. The protein-protein correlation network was employed to identify the important functional node protein MIC3, which was upregulated 5-fold in RH compared with TgCtwh3. MIC3 was experimentally confirmed to evoke a TNF-\u03b1 secretory response, and it also induced macrophage M1 polarization. This result suggests that MIC3 is a potentially useful immunomodulator that induces TNF-\u03b1 secretion and macrophage M1 polarization.<\/jats:p>","DOI":"10.1038\/srep39407","type":"journal-article","created":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T10:34:42Z","timestamp":1482316482000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Identification of a TNF-\u03b1 inducer MIC3 originating from the microneme of non-cystogenic, virulent Toxoplasma gondii"],"prefix":"10.1038","volume":"6","author":[{"given":"Jingfan","family":"Qiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delong","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,21]]},"reference":[{"key":"BFsrep39407_CR1","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.ijpara.2009.02.004","volume":"39","author":"LM Weiss","year":"2009","unstructured":"Weiss, L. 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