{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:40:37Z","timestamp":1790887237611,"version":"4.1.0"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI145096"],"award-info":[{"award-number":["R01 AI145096"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI145096"],"award-info":[{"award-number":["R01 AI145096"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI145096"],"award-info":[{"award-number":["R01 AI145096"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Trained immunity is a long-term functional reprogramming of innate cells that allows for the formation of immune memory akin to adaptive responses, but with a more rapid nonspecific response. We recently identified an anti-inflammatory trained immunity response, termed trained tolerogenic immunity (TTI), induced by low virulence\n                      <jats:italic toggle=\"yes\">Candida dubliniensis,<\/jats:italic>\n                      that protects against acute lethal polymicrobial sepsis via myeloid-derived suppressor cells (MDSCs). Trained immunity and MDSCs arise following hematopoietic stem and progenitor cell (HSPC) expansion in the bone marrow. Here, we show that\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      induces inoculum-dependent protection and HSPC expansion, whereas depletion of HSPCs following\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      immunization abrogates protection. We further show that myeloid progenitors and putative MDSCs are increased in the bone marrow following\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      immunization, and that HSPC depletion results in reduced MDSC influx into the peritoneal cavity following lethal challenge. Bone marrow cytokine analysis revealed that mediators associated with MDSC development and trafficking, including G-CSF, CXCL2, and CCL2, are upregulated following\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      immunization. Finally, we find that the C-type lectin receptor adaptor protein Card9 is required for\n                      <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                      -induced protection and HSPC expansion, but not fungal trafficking to the bone marrow. Taken together, these results suggest that Card9-dependent fungal recognition in the bone marrow drives myelopoiesis and the induction of immunosuppressive MDSCs that are protective against lethal inflammation and sepsis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Cells of the innate immune system can be \u201ctrained\u201d by inducers to have enhanced memory responses, a phenomenon known as trained immunity. We recently identified an anti-inflammatory training response that is induced by low virulence fungal species (i.e.,\n                        <jats:italic toggle=\"yes\">Candida dubliniensis<\/jats:italic>\n                        ) and is protective against acute lethal polymicrobial sepsis. Trained immunity inducers, including\n                        <jats:italic toggle=\"yes\">C. dubliniensis,<\/jats:italic>\n                        can access the bone marrow and direct hematopoietic responses. Here, we demonstrate that protection is correlated with\n                        <jats:italic toggle=\"yes\">C. dubliniensis<\/jats:italic>\n                        -induced bone marrow expansion, which directs a myeloid bias in the bone marrow and ultimately results in the expansion of protective myeloid-derived suppressor cells. Involvement of the C-type lectin receptor adaptor protein Card9 in the protective response suggests fungal recognition in the bone marrow drives this response. These findings offer new insights into how trained immunity inducers direct differential outcomes, which will inform the development of novel immunotherapeutics to exploit the full spectrum of trained immune responses.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02906-25","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T12:00:15Z","timestamp":1761912015000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Induction of myelopoiesis by\n                    <i>Candida dubliniensis<\/i>\n                    drives protective trained immunity against sepsis in a Card9-dependent manner"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5212-0432","authenticated-orcid":true,"given":"Shannon 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