{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T14:06:41Z","timestamp":1793801201629,"version":"4.6.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Neutrophils are critical as the first-line defense against fungal pathogens. Yet, previous studies indicate that neutrophil function is complex during<jats:italic>Cryptococcus neoformans (Cn)<\/jats:italic>infection. To better understand the role of neutrophils in acute pulmonary cryptococcosis, we analyzed neutrophil heterogeneity by single-cell transcriptional analysis of immune cells in the lung of<jats:italic>Cn<\/jats:italic>-infected mice from a published dataset. We identified neutrophils by reference-based annotation and identified two distinct neutrophil subsets generated during acute<jats:italic>Cn<\/jats:italic>infection: A subset with an oxidative stress signature (Ox-PMN) and another with enhanced cytokine gene expression (Cyt-PMN). Based on gene regulatory network and ligand-receptor analysis, we hypothesize that Ox-PMNs interact with the fungus and generate ROS, while Cyt-PMNs are longer-lived neutrophils that indirectly respond to<jats:italic>Cn<\/jats:italic>-derived ligands and cytokines to modulate cell-cell communication with dendritic cells and alveolar macrophages. Based on the data, we hypothesized that, during<jats:italic>in vivo<\/jats:italic>fungal infection, there is a division of labor in which each activated neutrophil becomes either Ox-PMN or Cyt-PMN.<\/jats:p>","DOI":"10.3389\/fimmu.2021.670574","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T07:50:44Z","timestamp":1619682644000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Single-Cell Transcriptional Heterogeneity of Neutrophils During Acute Pulmonary Cryptococcus neoformans Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"M. 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