{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:56:33Z","timestamp":1782280593668,"version":"3.54.5"},"posted":{"date-parts":[[2025,6,17]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Toxoplasma gondii<\/jats:italic>\n                  is a globally prevalent intracellular parasite that infects \u223c40 million Americans. The murine immune response to\n                  <jats:italic>Toxoplasma<\/jats:italic>\n                  relies on both toll-like receptor (TLR) 11\/12 and immunity related GTPase-mediated (IRGs) responses, which humans lack, making it unclear how the human immune response detects and responds to the parasite. We investigated whether human V\u03b39V\u03b42 T cells, which detect phosphoantigens through the BTN3A1 receptor, shape the early immune response to the parasite. Using primary human peripheral blood mononuclear cells (PBMCs), we show that V\u03b39V\u03b42 T cells are activated by\n                  <jats:italic>Toxoplasma<\/jats:italic>\n                  -infected cells in a BTN3A1- dependent manner leading to secretion of interferon gamma (IFN\u03b3) and tumor necrosis factor-alpha (TNF\u03b1). Additionally, these T cells potentiate IFN\u03b3 production by natural killer (NK) cells, likely via TNF\u03b1 and interleukin (IL)-12 produced during infection. Active parasite invasion is required to stimulate the IFN\u03b3 response, and inhibition of the host mevalonate pathway, which limits the synthesis of the phosphoantigen isopentenyl pyrophosphate (IPP), attenuates the cytokine response, indicating\n                  <jats:italic>Toxoplasma<\/jats:italic>\n                  infection increases host phosphoantigens leading to V\u03b39V\u03b42 T cell activation. Our findings identify V\u03b39V\u03b42 T cells as key effectors that potentiate NK cells in the early human immune response to\n                  <jats:italic>Toxoplasma<\/jats:italic>\n                  , bridging innate and adaptive immunity in the absence of TLR11\/12 signaling.\n                <\/jats:p>","DOI":"10.1101\/2025.06.12.659293","type":"posted-content","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T18:05:26Z","timestamp":1750183526000},"source":"Crossref","is-referenced-by-count":0,"title":["The early human interferon gamma response to\n                  <i>Toxoplasma gondii<\/i>\n                  is driven by V\u03b39V\u03b42 T-cell sensing of host phosphoantigens and subsequent NK-cell activation"],"prefix":"10.64898","author":[{"given":"Felipe","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-7109","authenticated-orcid":false,"given":"Jeroen P.J.","family":"Saeij","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041203523982000_2025.06.12.659293v1.1","first-page":"1","article-title":"Risk ranking of foodborne parasites: State of the art","volume":"8\u2013 9","year":"2017","journal-title":"Food Waterborne 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