{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:59:13Z","timestamp":1793336353060,"version":"4.5.0"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01AI141368-01A, R01 AI169769"],"award-info":[{"award-number":["R01AI141368-01A, R01 AI169769"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,10,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Fungal pathogens are underappreciated causes of significant morbidity and mortality worldwide. In previous studies, we determined that a heat-killed,\n              <jats:italic>Cryptococcus neoformans<\/jats:italic>\n              fbp1-deficient strain (HK-fbp1) is a potent vaccine candidate. We determined that vaccination with HK-fbp1 confers protective immunity against lethal Cryptococcosis in an interferon \u03b3 (IFN\u03b3)-dependent manner. In this study, we set out to uncover cellular sources and relevant targets of the protective effects of IFN\u03b3 in response to the HK-fbp1 vaccine. We found that early IFN\u03b3 production peaks at day 3 and that monocytes and neutrophils are important sources of this cytokine after vaccination. Neutralization of IFN\u03b3 at day 3 results in impaired CCR2\n              <jats:sup>+<\/jats:sup>\n              monocyte recruitment and reduced differentiation into monocyte-derived dendritic cells (Mo-DC). In turn, depletion of CCR2\n              <jats:sup>+<\/jats:sup>\n              cells prior to immunization results in impaired activation of IFN\u03b3-producing CD4 and CD8 T cells. Thus, monocytes are important targets of innate IFN\u03b3 and help promote further IFN\u03b3 production by lymphocytes. We employed monocyte-fate mapper and conditional STAT1 knockout mice to uncover that STAT1 activation in CD11c\n              <jats:sup>+<\/jats:sup>\n              cells, including alveolar macrophages, Mo-DCs, and monocyte-derived macrophages (Mo-Mac) is essential for HK-fbp1 vaccine-induced protection. Altogether, our aggregate findings suggest critical roles for innate cells as orchestrators of vaccine-induced protection against\n              <jats:italic>Cryptococcus<\/jats:italic>\n              infection.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The number of patients susceptible to invasive fungal infections across the world continues to rise at an alarming pace yet current antifungal drugs are often inadequate. Immune-based interventions and novel antifungal vaccines hold the promise of significantly improving patient outcomes. In previous studies, we identified a\n                <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                mutant strain (Fbp1-deficient) as a potent, heat-inactivated vaccine candidate capable of inducing homologous and heterologous antifungal protection. In this study, we used a combination of methods together with a cohort of conditional knockout mouse strains to interrogate the roles of innate cells in the orchestration of vaccine-induced antifungal protection. We uncovered novel roles for neutrophils and monocytes as coordinators of a STAT1-dependent cascade of responses that mediate vaccine-induced protection against invasive cryptococcosis. This new knowledge will help guide the future development of much-needed antifungal vaccines.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01944-24","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T13:01:02Z","timestamp":1727355662000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Innate cells and STAT1-dependent signals orchestrate vaccine-induced protection against invasive\n            <i>Cryptococcus<\/i>\n            infection"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4675-4083","authenticated-orcid":false,"given":"Keyi","family":"Wang","sequence":"first","affiliation":[{"name":"Graduate School of Biomedical Sciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, 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