{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:55:46Z","timestamp":1789955746848,"version":"4.0.1"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>\n                    is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that\n                    <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n                    interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by\n                    <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n                    was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, namely, the MHC-II-associated invariant chain (Ii or CD74) and the peptide editor H2-DM, in professional antigen-presenting cells (pAPCs). Genetic deletion of CD74 restored the ability of infected dendritic cells to present a parasite antigen in the context of MHC-II\n                    <jats:italic>in vitro<\/jats:italic>\n                    . CD74 mRNA and protein levels were, surprisingly, elevated in infected cells, whereas MHC-II and H2-DM expression was inhibited. CD74 accumulated mainly in the endoplasmic reticulum (ER), and this phenotype required live parasites, but not active replication. Finally, we compared the impacts of genetic deletion of CD74 and H2-DM genes on parasite dissemination toward lymphoid organs in mice, as well as activation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and interferon gamma (IFN-\u03b3) levels during acute infection. Cyst burdens and survival during the chronic phase of infection were also evaluated in wild-type and knockout mice. These results highlight the fact that the infection is influenced by multiple levels of parasite manipulation of the MHC-II antigen presentation pathway.\n                  <\/jats:p>","DOI":"10.1128\/iai.00415-15","type":"journal-article","created":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T22:04:50Z","timestamp":1437429890000},"page":"3865-3880","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection"],"prefix":"10.1128","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9736-1827","authenticated-orcid":false,"given":"Louis-Philippe","family":"Leroux","sequence":"first","affiliation":[{"name":"Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manami","family":"Nishi","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"El-Hage","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Fox","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Bzik","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence S.","family":"Dzierszinski","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, McGill University, Sainte-Anne-de-Bellevue, Qu\u00e9bec, Canada"},{"name":"Carleton University, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.167.3919.893"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.132.4.636"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2004.09.005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2307\/3284282"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/590149"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/15.2.211"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.4049\/jimmunol.146.1.286","article-title":"Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine","volume":"146","author":"Gazzinelli RT","year":"1991","unstructured":"Gazzinelli RT, Hakim FT, Hieny S, Shearer GM, Sher A. 1991. 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