{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:19:09Z","timestamp":1791839949740,"version":"4.3.4"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2023\/15407-0 , 2023\/17308-0 , 2023\/14310-3 , 2023\/08856-3, 2019\/10097-8"],"award-info":[{"award-number":["2023\/15407-0 , 2023\/17308-0 , 2023\/14310-3 , 2023\/08856-3, 2019\/10097-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by\n                    <jats:italic>Paracoccidioides<\/jats:italic>\n                    spp. It is endemic to the Americas, with the highest incidence reported in Brazil. Pulmonary involvement occurs in nearly all adult patients. The current standard of care relies on antifungal agents such as amphotericin B (AmB), itraconazole, and fluconazole. However, long-term treatment is often associated with poor patient adherence and sequelae, attributable to drug toxicity, chronic inflammation, and fibrosis, which can impair organ function. In this context, therapies that modulate the host immune response have gained prominence. Antibodies targeting the PD-1 immune checkpoint, a regulatory protein highly expressed on lymphocytes, represent a particularly promising strategy. Previous work from our group demonstrated that anti-PD-1 administration in\n                    <jats:italic>P. brasiliensis<\/jats:italic>\n                    -infected mice led to controlled disease, characterized by a reduced fungal burden and improved survival. Notably, this clinical improvement correlated with the preservation of protective Th1\/Th17 responses. Based on these findings, this study aimed to evaluate the efficacy of a combined therapy using anti-PD-1 alongside a conventional antifungal. We sought to assess its impact on host immune modulation and fungal clearance. To this end, C57BL\/6 mice were inoculated with 1\u00d710\n                    <jats:sup>6<\/jats:sup>\n                    <jats:italic>P. brasiliensis<\/jats:italic>\n                    yeast cells. After six weeks, the mice were treated with anti-PD-1, either alone or in combination with AmB. The disease course was evaluated for two weeks post-treatment through CFU counts, histological analysis, and survival monitoring. The host immune response in the lungs was characterized using ELISA and flow cytometry. Our results demonstrate that the anti-PD-1 + AmB combination led to superior disease control compared to monotherapies. This was evidenced by a significant reduction in fungal load, diminished pulmonary lesion size, and enhanced survival. Furthermore, the combined treatment promoted an increase in the pulmonary effector lymphocyte population while reducing overall cytokine levels, indicating effective pathogen control without excessive inflammation. Collectively, these data indicate that restoring an effective immune response via PD-1 blockade, in conjunction with the direct antifungal activity of AmB, results in superior control of PCM. This study provides a rationale for future research into immunomodulatory strategies as an adjunct to conventional antifungal treatment for PCM.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1769296","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:25:58Z","timestamp":1775107558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Combined anti-PD-1 and amphotericin B therapy reduces fungal burden and enhances control of murine paracoccidioidomycosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Nycolas Willian","family":"Preite","sequence":"first","affiliation":[{"name":"Institute of Science and Technology, Federal University of S\u00e3o Paulo","place":["S\u00e3o Jos\u00e9 dos Campos, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipe Nogueira","family":"Franco","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology, Federal University of S\u00e3o Paulo","place":["S\u00e3o Jos\u00e9 dos Campos, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Vieira","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology, Federal University of S\u00e3o Paulo","place":["S\u00e3o Jos\u00e9 dos Campos, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Soares dos Santos","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology, Federal University of S\u00e3o Paulo","place":["S\u00e3o Jos\u00e9 dos Campos, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral","family":"Molist-Homs","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology, Federal University of S\u00e3o Paulo","place":["S\u00e3o Jos\u00e9 dos Campos, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Montanari","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech University","place":["Blacksburg, VA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L\u00facia Garcia","family":"Calich","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo (USP)","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio Vieira","family":"Loures","sequence":"additional","affiliation":[{"name":"Institute of Science and Technology, Federal University of S\u00e3o Paulo","place":["S\u00e3o Jos\u00e9 dos Campos, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1590\/1806-3713\/e20180167","article-title":"Treatment compliance of patients with paracoccidioidomycosis in Central-West Brazil","volume":"45","author":"Andrade","year":"2019","journal-title":"J. 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