{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:18:27Z","timestamp":1791839907861,"version":"4.3.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cryptococcus neoformans, the etiologic agent of cryptococcosis, can survive and replicate within host immune cells, contributing to development of cryptococcal meningitis. Within the lung, C neoformans interacts with innate immune subsets, including macrophages and dendritic cells (DCs). Our previous work demonstrated that Ly6c\u2212 monocyte\u2013like macrophages restrict fungal proliferation, whereas CD11b+ DCs promote fungal growth. Transcriptomic profiling revealed differential expression of MHC-I gene H2-K1, calreticulin, and metabolic genes. Therefore, we hypothesized that H2-K1 and metabolic pathways modulate intracellular fungal fate within pulmonary macrophages and DCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>H2-K1 expression was knocked down by siRNA in J774 macrophages and bone marrow\u2013derived DCs induced by granulocyte-macrophage colony-stimulating factor. Antifungal activity was determined by colony-forming unit enumeration. Phagocytic uptake, cathepsin B activity, Nos2 expression, and reactive oxygen species production were quantified by flow cytometry. Metabolic dependencies were evaluated through SCENITH assay (single-cell energetic metabolism by profiling translational inhibition).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>H2-K1 knockdown in J774 cells significantly reduced antifungal activity as compared with controls. H2-K1 knockdown also decreased calreticulin gene expression, suggesting that H2-k1 has downstream effects in the pathway. H2-K1 silencing did not significantly alter phagocytic uptake, cathepsin B activity, or Nos2 expression. However, reactive oxygen species production was significantly reduced in H2-K1 knockdown J774 cells, indicating impaired responses. SCENITH analysis revealed that antifungal macrophages shift their metabolism toward glucose oxidation for ATP generation, which is important for antifungal activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings indicate that metabolic reprogramming is critical for effective antifungal responses. Our data provide a foundation for future studies aimed at targeting host immune and metabolic pathways to enhance antifungal immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag144","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:42:45Z","timestamp":1772714565000},"page":"e1500-e1510","source":"Crossref","is-referenced-by-count":1,"title":["MHC-I Upregulation and Increased Glucose Dependence Define Innate Antifungal Immune Responses to\n                    <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1093","volume":"233","author":[{"given":"Ayesha S","family":"Nair","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Oklahoma State University , Stillwater, Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-2146","authenticated-orcid":false,"given":"Karen 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