{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:54:39Z","timestamp":1780480479783,"version":"3.54.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>During <jats:italic>Trypanosoma cruzi<\/jats:italic> infection, the immune system activates a robust inflammatory response, involving cytokines and chemokines like IFN-\u03b3, TNF, IL-6, IL-1\u03b2, CCL2, and CCL5, to control parasite replication. The CX3CL1 chemokine and its receptor, CX3CR1, have been implicated in amplifying inflammation through pathways like NF-\u03baB, MAPKs, STATs, TLRs, and NLRs, contributing to tissue damage. This study evaluated the effects of blocking CX3CR1 with the allosteric antagonist AZD8797 in a murine model of acute <jats:italic>T. cruzi<\/jats:italic> infection. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL\/6 mice were infected with 10<jats:sup>3<\/jats:sup> trypomastigote forms of <jats:italic>T. cruzi<\/jats:italic> (Y strain) and received AZD8797 (10 mg\/kg) intraperitoneally for 10 days. On the 10th day, animals were euthanized and heart, skeletal muscle, and liver tissues were collected for CX3C L1 protein expression, biomarkers (IL-1\u03b2, IL-4, IL-6, IL-10, IL-15, IL-17, IFN-\u03b3, TNF, and CCL2) quantified by Cytometric Bead Array and Enzyme Immunoassay. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment reduced spleen mass and cardiac levels of CCL2 and IL-15, with an increase of IL-4. Conversely, in skeletal muscle, TNF, IL-6, and IL-10 increased, while IL-15 decreased. Liver tissue showed reduced IL-15, IL-6, and IL-1\u03b2 levels, alongside lowered plasma hepcidin and ferritin concentrations. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings highlight CX3CL1\u2019s site-specific role in modulating inflammation and iron metabolism during acute <jats:italic>T. cruzi<\/jats:italic> infection, suggesting its potential as a therapeutic target for infection management and disease prognosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1585883","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:14:30Z","timestamp":1756268070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of the CX3CL1\/CX3CR1 axis in iron metabolism and immune regulation during acute Trypanosoma cruzi 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