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No vaccine against Candida spp. or other fungal pathogens of humans is available. We recently discovered the Blastomyces Dectin-2 ligand endoglucanase 2 that harbors antigenic and adjuvant functions and can function as a protective vaccine against that fungus. We also reported that the adjuvant activity, which is mediated by O-mannans decorating the C terminus of Blastomyces Dectin-2 ligand endoglucanase 2, can augment peptide Ag-induced vaccine immunity against heterologous agents, including Cryptococcus, Candida, and influenza. In this article, we report that the O-linked mannans alone, in the absence of any antigenic peptide, can also protect against systemic candidiasis, reducing kidney fungal load and increasing survival in a Dectin-2\u2013dependent manner. We found that this long-term glycan-induced protection is mediated by innate lymphocyte populations including TCR-\u03b3\u03b4+ T cells, innate lymphoid cells, and NK cells that subsequently activate and release reactive oxygen species from neutrophils and monocytes. Our findings suggest that Blastomyces O-mannan displayed by Eng2 induces a form of protective trained immunity mediated by innate lymphocyte populations.<\/jats:p>","DOI":"10.4049\/jimmunol.2400065","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T09:18:53Z","timestamp":1723022333000},"page":"843-852","source":"Crossref","is-referenced-by-count":3,"title":["Vaccination with O-linked Mannans Protects against Systemic Candidiasis through Innate Lymphocyte Populations"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-2366","authenticated-orcid":false,"given":"Cleison Ledesma","family":"Taira","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"dos Santos Dias","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section, Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lichtenberger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0724-6292","authenticated-orcid":false,"given":"Alexander J","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-1001","authenticated-orcid":false,"given":"Brenda","family":"Kischkel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Nijmegen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , Nijmegen ,","place":["the Netherlands"]},{"name":"Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn , Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, WI"},{"name":"Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, WI"},{"name":"Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"W\u00fcthrich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2013Madison , Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"2026041420283716300_r1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.prp.2007.06.008","article-title":"Fungal infections of the heart: a clinicopathologic study of 50 autopsy cases","volume":"203","author":"Chinen","year":"2007","journal-title":"Pathol. 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