{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:01:01Z","timestamp":1753880461047,"version":"3.41.2"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01AI144016-01"],"award-info":[{"award-number":["R01AI144016-01"]}]},{"name":"HHS | National Institutes of Health","award":["T32 AI007414"],"award-info":[{"award-number":["T32 AI007414"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            While the asexual cycle of\n            <jats:italic>Toxoplasma gondii<\/jats:italic>\n            can occur in any warm-blooded animal, the sexual cycle is restricted to the feline intestine. We previously determined that because cats lack delta-6-desaturase activity in their intestines, they build up excess linoleic acid, which signals\n            <jats:italic>T. gondii<\/jats:italic>\n            to undergo sexual development. We hypothesized that\n            <jats:italic>T. gondii<\/jats:italic>\n            oxygenates linoleic acid to signal sexual development, so we examined the\n            <jats:italic>T. gondii<\/jats:italic>\n            genome for lipoxygenases-like enzymes (TgLOXL) enzymes. We identified seven TgLOXLs that were at least 100-fold more abundant in the cat intestinal versus the tissue culture tachyzoite stage. Parasites deleted in TgLOXL1 (Tg\u0394LOXL1) had no significant growth differences in tissue culture fibroblast cells. Because the sexual development assay begins with brain cysts, we infected mice with Tg\u0394LOXL1 and were surprised to find that Tg\u0394LOXL1 had reduced virulence. The Tg\u0394LOXL1 parasitemia was reduced by 3 d post-infection and largely cleared by 7 d post-infection. At 3 d post-infection, the cytokines interferon gamma (IFN-\u03b3), IL-6, MCP-1, and TNF-\u03b1 were significantly reduced in Tg\u0394LOXL1-infected mice, which prompted us to examine Tg\u0394LOXL1 in IFN-\u03b3 KO mice. We found that IFN-\u03b3 KO mice infected with Tg\u0394LOXL1 succumbed to acute infection with the same kinetics as the parental and complemented strains, suggesting that TgLOXL1 plays a role in the IFN-\u03b3 signaling cascade. In tissue culture fibroblasts, TgLOXL1 was localized within the parasite, but in leukocytes from infected mice and activated macrophages, TgLOXL1 was localized within the host cytoplasm. These results suggest that TgLOXL1 changes localization in response to host immune activation.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Lipoxygenases (LOXs) are enzymes that catalyze the deoxygenation of polyunsaturated fatty acids such as linoleic and arachidonic acid. These modifications create signaling molecules that are best characterized for modulating the immune response. Deletion of the first lipoxygenase-like enzyme characterized for\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              (TgLOXL1) generated a less virulent strain, and infected mice showed a decreased immune response. This virulence defect was dependent on the mouse cytokine interferon gamma IFN\u03b3. TgLOXL1 changes location from inside the parasite in tissue culture conditions to vesicular structures within the host immune cells during mouse infection. These results suggest that TgLOXL1 plays a role in the modification of the host immune response in mice.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01279-23","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T13:03:02Z","timestamp":1693400582000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["A\n            <i>Toxoplasma gondii<\/i>\n            lipoxygenase-like enzyme is necessary for virulence and changes localization associated with the host immune response"],"prefix":"10.1128","volume":"14","author":[{"given":"Carlos J.","family":"Ram\u00edrez-Flores","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison , Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Billy Joel","family":"Erazo Flores","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison , Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s M.","family":"Tibabuzo Perdomo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison , Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie L.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison , Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison , Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Mendoza Cavazos","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison , Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9362-8088","authenticated-orcid":false,"given":"Laura J.","family":"Knoll","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison , Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090203"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.6.2988"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.6.2533"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3128869"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14587"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-515250-1.50021-7"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-091906-5.00008-2"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00225"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92120-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni745"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021183"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00565-08"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","unstructured":"Di Genova BM Wilson SK Dubey JP Knoll LJ . 2019. 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