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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Visceral leishmaniasis (VL) occurs more frequently in immunosuppressed individuals, especially those undergoing immunosuppressive drug therapy for an autoimmune disease. In those receiving TNF antagonist therapy (anti-TNF), the course of VL is more severe and the response to traditional leishmanicidal treatments, such as antimonials (Sb), is often reduced. This effect of anti-TNF treatment is observed in our immunosuppressed-mouse model of VL. In this model, we compared anti-TNF immunosuppression with no immunosuppression before and after VL treatment with Sb.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum-derived extracellular vesicles (EVs) were analyzed through label-free quantitative proteomics to identify proteins involved in both VL severity and the impact of anti-TNF immunosuppression on treatment outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 223 dysregulated proteins were found in the pre-treatment groups, the majority of which, such as vitronectin, haemopexin or caveolin-1, were downregulated in the anti-TNF samples. In contrast, 173 proteins were identified in the Sb-treatment groups, most of which were found enriched in the anti-TNF plus treatment samples (anti-TNF+Sb) including fibronectin, transferrin, vitronectin and dipeptidyl peptidase-4. These differentially-expressed proteins were associated with pathways related to the immune system, liver regeneration, and ion transport.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings have useful implications for the clinical management of VL patients under anti-TNF immunosuppression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1634080","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T04:13:29Z","timestamp":1753848809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Protein dysregulation during Leishmania infantum infection in anti-TNF immunosuppressed mice revealed through quantitative proteomics analysis of extracellular vesicles"],"prefix":"10.3389","volume":"16","author":[{"given":"Lorena","family":"Bernardo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Montero-Calle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Carlos","family":"Solana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Lozano-Rendal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Torres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Barderas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Carrillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"B1","volume-title":"Manual on case management and surveillance of the leishmaniases in the WHO European Region","author":"Gradoni","year":"2017"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1590\/s1678-9946202062028","article-title":"A comprehensive systematic review of leishmaniasis in patients undergoing drug-induced immunosuppression for the treatment of dermatological, rheumatological and gastroenterological diseases","volume":"62","author":"Kurizky","year":"2020","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007708","article-title":"Leishmaniasis and tumor necrosis factor alpha antagonists in the Mediterranean basin. 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