{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T23:04:33Z","timestamp":1779663873319,"version":"3.53.1"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":128,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1800200"],"award-info":[{"award-number":["2022YFD1800200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YDZX2026009"],"award-info":[{"award-number":["YDZX2026009"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transboundary and Emerging Diseases"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    establishes infection in hosts by deploying effector proteins that reprogram cytokine\u2010driven immunity. While protozoan parasite\u2010encoded macrophage migration inhibitory factor (MIF) homologs exemplify cytokine mimicry, whether\n                    <jats:italic>T. gondii<\/jats:italic>\n                    targets additional host cytokine axes remains unclear. Here, we identify a\n                    <jats:italic>T. gondii<\/jats:italic>\n                    3\u2010ketoacyl\u2010CoA reductase (KCR) as a noncanonical cytokine modulator that engages the granulocyte\u2010macrophage colony\u2010stimulating factor (CSF2) receptor alpha chain (CSF2R\u03b1). In HEK293T cells, forward and reverse co\u2010immunoprecipitation (Co\u2010IP) assays demonstrated a specific interaction between KCR and murine CSF2R\u03b1. The recombinant KCR triggered rapid activation of canonical CSF2 signaling in RAW264.7 macrophages, inducing phosphorylation of JAK2 and STAT5 to levels comparable to murine CSF2. Functionally, KCR enhanced NADPH oxidase\u2010dependent oxidative responses, increasing intracellular reactive oxygen species (ROS) and upregulating transcripts encoding core oxidase subunits, including CYBB, CYBA, NCF1, and NCF2. KCR also promoted phagocytic capacity, elevating FITC\u2010dextran uptake and inducing expression of complement, Fc, and scavenger receptor genes, including CR3, CD16, CD64, MSR1, and MARCO. Notably, KCR pretreatment attenuated CSF2\u2010induced JAK2\/STAT5 phosphorylation, ROS production, and phagocytosis, consistent with competitive interference with endogenous CSF2\u2010CSF2R signaling. Together, these findings reveal KCR as a previously unrecognized\n                    <jats:italic>T. gondii<\/jats:italic>\n                    factor that targets the CSF2\/CSF2R axis to recalibrate macrophage effector functions, expanding the repertoire of parasite strategies for cytokine pathway modulation and highlighting CSF2\u2010CSF2R signaling as a potential interface for mechanistic and therapeutic investigation in toxoplasmosis.\n                  <\/jats:p>","DOI":"10.1155\/tbed\/8426765","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T23:01:13Z","timestamp":1778367673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Toxoplasma gondii<\/i>\n                    KCR is a Noncanonical Modulator of CSF2 Signaling that Targets the CSF2R\u03b1\u2013JAK2\/STAT5 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