{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:59:23Z","timestamp":1787763563215,"version":"build-2784847793"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018106","name":"Louisiana Clinical and Translational Science Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018106","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010519","name":"Health Sciences Center New Orleans, Louisiana State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010519","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Fungal-bacterial intra-abdominal infections (IAI) can lead to sepsis with significant morbidity and mortality. We have established a murine model of <jats:italic>Candida albicans<\/jats:italic> (<jats:italic>Ca<\/jats:italic>) and <jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>Sa<\/jats:italic>) IAI that results in acute lethal sepsis. Prior intraperitoneal or intravenous inoculation with low virulence <jats:italic>Candida dubliniensis (Cd)<\/jats:italic> confers high level protection against lethal <jats:italic>Ca\/Sa<\/jats:italic> IAI and sepsis. Protection <jats:italic>via Cd<\/jats:italic> immunization is associated with decreased pro-inflammatory cytokines and mediated by Gr-1<jats:sup>+<\/jats:sup> putative myeloid-derived suppressor cells (MDSCs) representing a novel form of trained innate immunity (TII). The objective of these studies was to determine the extent of <jats:italic>Cd<\/jats:italic>-mediated TII against sepsis of broad origin and explore the potential of fungal cell wall components as abiotic immunogen alternatives to induce TII, including zymosan depleted of TLR2 activity (d-zymosan), or purified preparations of \u03b2-glucan. Immunized mice were challenged 14 days post-immunization with a lethal array of live or abiotic inducers of sepsis, including <jats:italic>Ca\/Sa, Ca<\/jats:italic>\/<jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>Ca\/Ec<\/jats:italic>), LPS or untreated zymosan. Results showed that live <jats:italic>Cd<\/jats:italic> immunization was protective against sepsis induced by <jats:italic>Ca\/Ec<\/jats:italic> and zymosan, but not LPS. Similar to protection against Ca\/Sa, survival was dependent on Gr-1+ cells with no role for macrophages. Among the fungal cell wall compounds as immunogens, immunization with d-zymosan and an alkali-treated form of \u03b2-glucan also resulted in significant protection against sepsis induced by <jats:italic>Ca\/Sa<\/jats:italic> or <jats:italic>Ca\/Ec<\/jats:italic>, but not LPS sepsis. Again, there was a strong dependence on Gr-1+ cells for protection with one exception, an added role for macrophages in the case of protection induced by alkali-treated \u03b2-glucan. Overall, these results demonstrate that immunization with <jats:italic>Cd<\/jats:italic> as well as abiotic fungal cell components are capable of Gr-1+ cell-mediated trained innate immune protection against sepsis of broad microbial origin. In addition, abiotic \u03b2-glucans represent potential alternatives to live <jats:italic>Cd<\/jats:italic> for protection against lethal polymicrobial sepsis.<\/jats:p>","DOI":"10.3389\/fcimb.2022.898030","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T04:31:46Z","timestamp":1655094706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Efficacy of Candida dubliniensis and Fungal \u03b2-Glucans in Inducing Trained Innate Immune Protection Against Inducers of Sepsis"],"prefix":"10.3389","volume":"12","author":[{"given":"Amanda J.","family":"Harriett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Esher Righi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Lilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Paul","family":"Fidel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairi C.","family":"Noverr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/j.cmi.2019.08.011","article-title":"Developing the Concept of Beneficial Non-Specific Effect of Live Vaccines With Epidemiological Studies","volume":"25","author":"Aaby","year":"2019","journal-title":"Clin. 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