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MDSC suppressive activity on Th1\/Th17 immunity was shown to be mediated by inhibitory effect of IL-10, IDO-1, and PD-L1. Studies revealed the 5-fluorouracil (5-FU) as a selective MDSC apoptosis-inducing agent, but its in vivo effect on infectious processes remains poorly investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MDSCs and other leukocytes were evaluated in the lungs of 5-FU\u2013treated mice after 4, 6, and 8 weeks of Paracoccidioides brasiliensis infection. Disease severity and immunological response were evaluated in MDSCs-depleted mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>5-FU treatment caused a reduction of pulmonary MDSCs and fungal loads. The specific depletion of MDSCs reduced all pulmonary CD4+ T-cell populations resulting in improved tissue pathology and increased survival. This reduction was concomitant with increased frequencies of Th1\/Th17 cells and the increased levels of Th1\/Th2\/Th17 cytokines in the lungs and liver of treated mice, suggesting an early and efficient protective effect of these cells. Furthermore, the immune protection conferred by the 5-FU treatment could be reversed by the MDSC-adoptive transfer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>5-FU depletes MDSCs of P. brasiliensis-infected mice, resulting in enhanced immunity. This protective effect can be viewed as a potential immunotherapeutic tool for PCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiae350","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T18:10:18Z","timestamp":1720548618000},"page":"1279-1290","source":"Crossref","is-referenced-by-count":10,"title":["Specific Depletion of Myeloid-Derived Suppressor Cells by the Chemotherapy Agent 5-Fluorouracil Enhances Protective Immune Response in Paracoccidioidomycosis"],"prefix":"10.1093","volume":"230","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9996-0105","authenticated-orcid":false,"given":"Nycolas Willian","family":"Preite","sequence":"first","affiliation":[{"name":"Institute of Science and Technology, Federal University of S\u00e3o Paulo , S\u00e3o Jos\u00e9 dos Campos 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