{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:59:10Z","timestamp":1776128350479,"version":"3.50.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100005302","name":"UofI | University of Illinois at Urbana-Champaign","doi-asserted-by":"publisher","award":["Institutional funds"],"award-info":[{"award-number":["Institutional funds"]}],"id":[{"id":"10.13039\/100005302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Rats vary in their susceptibilities to<jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>infection depending on the rat strain. Compared to the<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>-susceptible Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>. Thus, these two rat strains are ideal models for elucidating host mechanisms that are important for host resistance to<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>infection. Therefore, in our efforts to unravel molecular factors directing the protective early innate immune response in the LEW rat, we performed RNA sequencing analysis of the LEW versus BN rat with or without<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>infection. We identified three candidate small<jats:underline>G<\/jats:underline>TPase<jats:underline>im<\/jats:underline>munity-<jats:underline>a<\/jats:underline>ssociated<jats:underline>p<\/jats:underline>roteins (GIMAPs) that were upregulated (false discovery rate, 0.05) in the LEW rat in response to<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>infection. Subsequently, we engineered<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>-susceptible NR8383 rat macrophage cells for overexpression of LEW rat-derived candidate GIMAP 4, 5, and 6. By immunofluorescence analysis we observed that GIMAP 4, 5, and 6 in<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>-infected NR8383 cells each colocalized with GRA5, a parasite parasitophorous vacuole membrane (PVM) marker protein, suggesting their translocation to the PVM. Interestingly, overexpression of each candidate GIMAP in<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>-infected NR8383 cells induced translocation of LAMP1, a lysosome marker protein, to the<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>surface membrane. Importantly, overexpression of GIMAP 4, 5, or 6 individually inhibited intracellular<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>growth, with GIMAP 4 having the highest inhibitory effect. Together, our findings indicate that upregulation of GIMAP 4, 5, and 6 contributes to the robust refractoriness of the LEW rat to<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>through induction of lysosomal fusion to the otherwise nonfusogenic PVM.<\/jats:p>","DOI":"10.1128\/iai.00582-17","type":"journal-article","created":{"date-parts":[[2018,1,27]],"date-time":"2018-01-27T11:30:39Z","timestamp":1517052639000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Small GTPase Immunity-Associated Proteins Mediate Resistance to Toxoplasma gondii Infection in Lewis Rat"],"prefix":"10.1128","volume":"86","author":[{"given":"Chi Yong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana\u2014Champaign, Urbana, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana\u2014Champaign, Urbana, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H.","family":"Witola","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana\u2014Champaign, Urbana, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16412-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1547"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.06.022"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156255"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)32242-7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.4049\/jimmunol.161.12.6715","article-title":"Two families of GTPases dominate the complex cellular response to IFN-gamma","volume":"161","author":"Boehm U","year":"1998","unstructured":"Boehm U, Guethlein L, Klamp T, Ozbek K, Schaub A, Futterer A, Pfeffer K, Howard JC. 1998. 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