{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:18:28Z","timestamp":1791839908976,"version":"4.3.4"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103648, 1P20GM134973-01"],"award-info":[{"award-number":["P20GM103648, 1P20GM134973-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007069","name":"Oklahoma State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>With over 220,000 cases and 180,000 deaths annually, <jats:italic>Cryptococcus neoformans<\/jats:italic> is the most common cause of fungal meningitis and a leading cause of death in HIV\/AIDS patients in Sub-Saharan Africa. Either <jats:italic>C. neoformans<\/jats:italic> can be killed by innate airway phagocytes, or it can survive intracellularly. Pulmonary murine macrophage and dendritic cell (DC) subsets have been identified in the na\u00efve lung, and we hypothesize that each subset has different interactions with <jats:italic>C. neoformans<\/jats:italic>. For these studies, we purified murine pulmonary macrophage and DC subsets from na\u00efve mice \u2013 alveolar macrophages, Ly6c<jats:sup>-<\/jats:sup> and Ly6c<jats:sup>+<\/jats:sup> monocyte-like macrophages, interstitial macrophages, CD11b<jats:sup>+<\/jats:sup> and CD103<jats:sup>+<\/jats:sup> DCs. With each subset, we examined cryptococcal association (binding\/internalization), fungicidal activity, intracellular fungal morphology, cytokine secretion and transcriptional profiling in an <jats:italic>ex vivo<\/jats:italic> model using these pulmonary phagocyte subsets. Results showed that all subsets associate with <jats:italic>C. neoformans<\/jats:italic>, but only female Ly6c<jats:sup>-<\/jats:sup> monocyte-like macrophages significantly inhibited growth, while male CD11b<jats:sup>+<\/jats:sup> DCs significantly enhanced fungal growth. In addition, cytokine analysis revealed that some subsets from female mice produced increased amounts of cytokines compared to their counterparts in male mice following exposure to <jats:italic>C. neoformans<\/jats:italic>. In addition, although cells were analyzed <jats:italic>ex vivo<\/jats:italic> without the influence of the lung microenviroment, we did not find evidence of phagocyte polarization following incubation with <jats:italic>C. neoformans<\/jats:italic>. Imaging flow cytometry showed differing ratios of cryptococcal morphologies, c-shaped or budding, depending on phagocyte subset. RNA sequencing analysis revealed the up- and down-regulation of many genes, from immunological pathways (including differential regulation of MHC class I in the antigen processing pathway and the cell adhesion pathway) and pathways relating to relating to metabolic activity (genes in the Cytochrome P450 family, genes related to actin binding, calcium voltage channels, serine proteases, and phospholipases). Future studies gaining a more in-depth understanding on the functionality of individual genes and pathways specific to permissive and non-permissive pulmonary phagocytes will allow identification of key targets when developing therapeutic strategies to prevent cryptococcal meningitis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.722500","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T05:13:48Z","timestamp":1632806028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Transcriptional Changes in Pulmonary Phagocyte Subsets Dictate the Outcome Following Interaction With The Fungal Pathogen Cryptococcus neoformans"],"prefix":"10.3389","volume":"12","author":[{"given":"Ashlee N.","family":"Hawkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Brenden F.","family":"Determann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin N.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Wozniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"a019760","DOI":"10.1101\/cshperspect.a019760","article-title":"Cryptococcus Neoformans and Cryptococcus Gattii, the Etiologic Agents of Cryptococcosis","volume":"4","author":"Kwon-Chung","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92283-N","article-title":"Ecology, Life Cycle, and Infectious Propagule of Cryptococcus Neoformans","volume":"336","author":"Ellis","year":"1990","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5520(02)00036-3","article-title":"Cryptococcosis","volume":"16","author":"Perfect","year":"2002","journal-title":"Infect Dis Clin N Am"},{"key":"B4","doi-asserted-by":"publisher","first-page":"583","DOI":"10.4049\/jimmunol.1700958","article-title":"The Outcome of the Cryptococcus Neoformans-Macrophage Interaction Depends on Phagolysosomal Membrane Integrity","volume":"201","author":"De Leon-Rodriguez","year":"2018","journal-title":"J Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00272","article-title":"First Line of Defense: Innate Cell-Mediated Control of Pulmonary Aspergillosis","volume":"7","author":"Espinosa","year":"2016","journal-title":"Front Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuv018","article-title":"The Innate Immune Response to Aspergillus Fumigatus at the Alveolar Surface","volume":"39","author":"Margalit","year":"2015","journal-title":"FEMS Microbiol Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4585-4592.2000","article-title":"Role of Pulmonary Alveolar Macrophages in Defense of the Lung Against Pseudomonas Aeruginosa","volume":"68","author":"Cheung","year":"2000","journal-title":"Infect Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.005","article-title":"Lung Homeostasis: Influence of Age, Microbes, and the Immune System","volume":"46","author":"Lloyd","year":"2017","journal-title":"Immunity"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400318","article-title":"STAT1 Signaling Is Essential for Protection Against Cryptococcus Neoformans Infection in Mice","volume":"193","author":"Leopold Wager","year":"2014","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00935-15","article-title":"STAT1 Signaling Within Macrophages is Required for Antifungal Activity Against Cryptococcus Neoformans","volume":"83","author":"Leopold Wager","year":"2015","journal-title":"Infect Immun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e1007358","DOI":"10.1371\/journal.ppat.1007358","article-title":"IFN-Gamma Immune Priming of Macrophages In Vivo Induces Prolonged STAT1 Binding and Protection Against Cryptococcus Neoformans","volume":"14","author":"Leopold Wager","year":"2018","journal-title":"PloS Pathog"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090634","article-title":"Pulmonary Infection With an Interferon-Gamma-Producing Cryptococcus Neoformans Strain Results in Classical Macrophage Activation and Protection","volume":"176","author":"Hardison","year":"2010","journal-title":"Am J Pathol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103455","article-title":"Protective Immunity Against Pulmonary Cryptococcosis is Associated With STAT1-Mediated Classical Macrophage Activation","volume":"189","author":"Hardison","year":"2012","journal-title":"J Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501512","article-title":"Local GM-CSF-Dependent Differentiation and Activation of Pulmonary Dendritic Cells and Macrophages Protect Against Progressive Cryptococcal Lung Infection in Mice","volume":"196","author":"Chen","year":"2016","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00454-09","article-title":"Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense Against Pulmonary Infection With Cryptococcus Neoformans","volume":"77","author":"Osterholzer","year":"2009","journal-title":"Infect Immun"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00317-06","article-title":"In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis","volume":"74","author":"Wozniak","year":"2006","journal-title":"Infect Immun"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00105","article-title":"Cryptococcus and Phagocytes: Complex Interactions That Influence Disease Outcome","volume":"7","author":"Leopold Wager","year":"2016","journal-title":"Front Microbiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00660-08","article-title":"Cryptococcus Neoformans Enters the Endolysosomal Pathway of Dendritic Cells and Is Killed by Lysosomal Components","volume":"76","author":"Wozniak","year":"2008","journal-title":"Infect Immun"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.1.592-598.2005","article-title":"Opsonic Requirements for Dendritic Cell-Mediated Responses to Cryptococcus Neoformans","volume":"73","author":"Kelly","year":"2005","journal-title":"Infect Immun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.5.1201-1209.1990","article-title":"Growth Inhibition of Cryptococcus Neoformans by Cultured Human Monocytes: Role of the Capsule, Opsonins, the Culture Surface, and Cytokines","volume":"58","author":"Levitz","year":"1990","journal-title":"Infect Immun"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.46.6.521","article-title":"Phagocytosis and Killing of Cryptococcus Neoformans by Rat Alveolar Macrophages in the Absence of Serum","volume":"46","author":"Bolanos","year":"1989","journal-title":"J Leukocyte Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/02681218980000301","article-title":"Killing of Cryptococcus Neoformans by Rat Alveolar Macrophages","volume":"27","author":"Bolanos","year":"1989","journal-title":"J Med Vet Mycol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/02681218980000291","article-title":"Phagocytosis of Cryptococcus Neoformans by Rat Alveolar Macrophages","volume":"27","author":"Bolanos","year":"1989","journal-title":"J Med Vet Mycol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/136.5.1242","article-title":"Growth Inhibition of Cryptococcus Neoformans by Human Alveolar Macrophages","volume":"136","author":"Weinberg","year":"1987","journal-title":"Am Rev Respir Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104653","article-title":"The Intracellular Life of Cryptococcus Neoformans","volume":"9","author":"Coelho","year":"2014","journal-title":"Annu Rev Pathol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3390\/jof4010025","article-title":"Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus Neoformans","volume":"4","author":"Denham","year":"2018","journal-title":"J Fungi (Basel)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(01)02035-2","article-title":"Intracellular Parasitism of Macrophages by Cryptococcus Neoformans","volume":"9","author":"Feldmesser","year":"2001","journal-title":"Trends Microbiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12067","article-title":"Cryptococcus Interactions With Macrophages: Evasion and Manipulation of the Phagosome by a Fungal Pathogen","volume":"15","author":"Johnston","year":"2013","journal-title":"Cell Microbiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115027","article-title":"Binding of Cryptococcus Neoformans by Human Cultured Macrophages. Requirements for Multiple Complement Receptors and Actin","volume":"87","author":"Levitz","year":"1991","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.3.903-908.1997","article-title":"Variables Affecting Production of Monocyte Chemotactic Factor 1 From Human Leukocytes Stimulated With Cryptococcus Neoformans","volume":"65","author":"Levitz","year":"1997","journal-title":"Infect Immun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4225-4237.2000","article-title":"Cryptococcus Neoformans Is a Facultative Intracellular Pathogen in Murine Pulmonary Infection","volume":"68","author":"Feldmesser","year":"2000","journal-title":"Infect Immun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052702799","article-title":"Replication of Cryptococcus Neoformans in Macrophages is Accompanied by Phagosomal Permeabilization and Accumulation of Vesicles Containing Polysaccharide in the Cytoplasm","volume":"99","author":"Tucker","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.09.061","article-title":"Phagosome Extrusion and Host-Cell Survival After Cryptococcus Neoformans Phagocytosis by Macrophages","volume":"16","author":"Alvarez","year":"2006","journal-title":"Curr Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e1001041","DOI":"10.1371\/journal.ppat.1001041","article-title":"The Human Fungal Pathogen Cryptococcus Neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That is Inhibited by Arp2\/3 Complex-Mediated Actin Polymerisation","volume":"6","author":"Johnston","year":"2010","journal-title":"PloS Pathog"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01065-08","article-title":"Evidence of a Role for Monocytes in Dissemination and Brain Invasion by Cryptococcus Neoformans","volume":"77","author":"Charlier","year":"2009","journal-title":"Infect Immun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00587-07","article-title":"Depletion of Alveolar Macrophages Decreases the Dissemination of a Glucosylceramide-Deficient Mutant of Cryptococcus Neoformans in Immunodeficient Mice","volume":"75","author":"Kechichian","year":"2007","journal-title":"Infect Immun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2229-2239.2004","article-title":"Role of Extracellular Phospholipases and Mononuclear Phagocytes in Dissemination of Cryptococcosis in a Murine Model","volume":"72","author":"Santangelo","year":"2004","journal-title":"Infect Immun"},{"key":"B38","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.micinf.2015.08.017","article-title":"Cryptococcal Transmigration Across a Model Brain Blood-Barrier: Evidence of the Trojan Horse Mechanism and Differences Between Cryptococcus Neoformans Var. Grubii Strain H99 and Cryptococcus Gattii Strain R265","volume":"18","author":"Sorrell","year":"2016","journal-title":"Microbes Infect"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nature13989","article-title":"Tissue-Resident Macrophages Originate From Yolk-Sac-Derived Erythro-Myeloid Progenitors","volume":"518","author":"Gomez Perdiguero","year":"2015","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.017","article-title":"Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop Into Functional Tissue-Resident Macrophages","volume":"44","author":"van de Laar","year":"2016","journal-title":"Immunity"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2705","article-title":"Tissue-Resident Macrophages","volume":"14","author":"Davies","year":"2013","journal-title":"Nat Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/imm.12888","article-title":"Human Dendritic Cell Subsets: An Update","volume":"154","author":"Collin","year":"2018","journal-title":"Immunology"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131199","article-title":"Alveolar Macrophages Develop From Fetal Monocytes That Differentiate Into Long-Lived Cells in the First Week of Life via GM-CSF","volume":"210","author":"Guilliams","year":"2013","journal-title":"J Exp Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.03.011","article-title":"C-Myb(+) Erythro-Myeloid Progenitor-Derived Fetal Monocytes Give Rise to Adult Tissue-Resident Macrophages","volume":"42","author":"Hoeffel","year":"2015","journal-title":"Immunity"},{"key":"B45","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/ni.3052","article-title":"The Development and Function of Lung-Resident Macrophages and Dendritic Cells","volume":"16","author":"Kopf","year":"2015","journal-title":"Nat Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.immuni.2014.06.013","article-title":"Origin and Functions of Tissue Macrophages","volume":"41","author":"Epelman","year":"2014","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.620510","article-title":"Function of Macrophages in Disease: Current Understanding on Molecular Mechanisms","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2467","article-title":"Re(de)fining the Dendritic Cell Lineage","volume":"13","author":"Satpathy","year":"2012","journal-title":"Nat Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060595","article-title":"Role of Granulocyte Macrophage Colony-Stimulating Factor in Host Defense Against Pulmonary Cryptococcus Neoformans Infection During Murine Allergic Bronchopulmonary Mycosis","volume":"170","author":"Chen","year":"2007","journal-title":"Am J Pathol"},{"key":"B50","article-title":"Characterization of Pulmonary Interstitial Macrophage Phenotypes in a Mouse Model of Asthma","volume":"35","author":"Liu","year":"2014","journal-title":"Med J Wuhan Univ"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20064","article-title":"Accurate and Simple Discrimination of Mouse Pulmonary Dendritic Cell and Macrophage Populations by Flow Cytometry: Methodology and New Insights","volume":"61","author":"Vermaelen","year":"2004","journal-title":"Cytometry A"},{"key":"B52","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1165\/rcmb.2016-0361OC","article-title":"Three Unique Interstitial Macrophages in the Murine Lung at Steady State","volume":"57","author":"Gibbings","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200495","article-title":"Systemic Analysis of PPARgamma in Mouse Macrophage Populations Reveals Marked Diversity in Expression With Critical Roles in Resolution of Inflammation and Airway Immunity","volume":"189","author":"Gautier","year":"2012","journal-title":"J Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129122","article-title":"Developmental Origin of Lung Macrophage Diversity","volume":"143","author":"Tan","year":"2016","journal-title":"Development"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0366MA","article-title":"Identification of Myeloid Cell Subsets in Murine Lungs Using Flow Cytometry","volume":"49","author":"Zaynagetdinov","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0086MA","article-title":"Flow Cytometric Analysis of Macrophages and Dendritic Cell Subsets in the Mouse Lung","volume":"49","author":"Misharin","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0311134","article-title":"Lung Dendritic Cells at the Innate-Adaptive Immune Interface","volume":"90","author":"Condon","year":"2011","journal-title":"J Leukoc Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nri746","article-title":"Mouse and Human Dendritic Cell Subtypes","volume":"2","author":"Shortman","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00652","article-title":"Redefining Myeloid Cell Subsets in Murine Spleen","volume":"6","author":"Hey","year":"2015","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00037","article-title":"Pulmonary Macrophage and Dendritic Cell Responses to Cryptococcus Neoformans","volume":"10","author":"Nelson","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9167-9_9","article-title":"Depletion and Reconstitution of Macrophages in Mice","volume":"1960","author":"Kozicky","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901089","article-title":"Alveolar Macrophages Transport Pathogens to Lung Draining Lymph Nodes","volume":"183","author":"Kirby","year":"2009","journal-title":"J Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-013-0165-7","article-title":"Macrophage Cryptococcus Interactions: An Update","volume":"8","author":"Mansour","year":"2014","journal-title":"Curr Fungal Infect Rep"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00039-10","article-title":"Cryptococcal Interactions With the Host Immune System","volume":"6","author":"Voelz","year":"2010","journal-title":"Eukaryot Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31930","article-title":"Phenotypic non-Equivalence of Murine (Monocyte-) Macrophage Cells in Biomaterial and Inflammatory Models","author":"Chamberlain","year":"2009","journal-title":"J Biomed Materials Res Part A"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00297-09","article-title":"Cytokine Signaling Regulates the Outcome of Intracellular Macrophage Parasitism by Cryptococcus Neoformans","volume":"77","author":"Voelz","year":"2009","journal-title":"Infect Immun"},{"key":"B67","doi-asserted-by":"publisher","first-page":"e0194615","DOI":"10.1371\/journal.pone.0194615","article-title":"Quantifying Donor-to-Donor Variation in Macrophage Responses to the Human Fungal Pathogen Cryptococcus Neoformans","volume":"13","author":"Garelnabi","year":"2018","journal-title":"PloS One"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600777","article-title":"Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets","volume":"198","author":"Patel","year":"2017","journal-title":"J Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20172020","article-title":"Growth of Mycobacterium Tuberculosis In Vivo Segregates With Host Macrophage Metabolism and Ontogeny","volume":"215","author":"Huang","year":"2018","journal-title":"J Exp Med"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/microbiolspec.BAI-0001-2019","article-title":"Mycobacterium Tuberculosis: Bacterial Fitness Within the Host Macrophage","volume":"7","author":"Huang","year":"2019","journal-title":"Microbiol Spectr"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.12.005","article-title":"Immune Regulation by Monocytes","volume":"35","author":"Murray","year":"2018","journal-title":"Semin Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.2021","article-title":"CCR2 Expression Determines T1 Versus T2 Polarization During Pulmonary Cryptococcus Neoformans Infection","volume":"164","author":"Traynor","year":"2000","journal-title":"J Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.610","article-title":"CCR2 Mediates Conventional Dendritic Cell Recruitment and the Formation of Bronchovascular Mononuclear Cell Infiltrates in the Lungs of Mice Infected With Cryptococcus Neoformans","volume":"181","author":"Osterholzer","year":"2008","journal-title":"J Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080673","article-title":"Cryptococcal Urease Promotes the Accumulation of Immature Dendritic Cells and a non-Protective T2 Immune Response Within the Lung","volume":"174","author":"Osterholzer","year":"2009","journal-title":"Am J Pathol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.ajpath.2010.11.006","article-title":"Chemokine Receptor 2-Mediated Accumulation of Fungicidal Exudate Macrophages in Mice That Clear Cryptococcal Lung Infection","volume":"178","author":"Osterholzer","year":"2011","journal-title":"Am J Pathol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"e1007627","DOI":"10.1371\/journal.ppat.1007627","article-title":"Inflammatory Monocytes are Detrimental to the Host Immune Response During Acute Infection With Cryptococcus Neoformans","volume":"15","author":"Heung","year":"2019","journal-title":"PloS Pathog"},{"key":"B77","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3390\/jof4010036","article-title":"Interactions of Cryptococcus With Dendritic Cells","volume":"4","author":"Wozniak","year":"2018","journal-title":"J Fungi (Basel)"},{"key":"B78","doi-asserted-by":"publisher","first-page":"e6854","DOI":"10.1371\/journal.pone.0006854","article-title":"Insights Into the Mechanisms of Protective Immunity Against Cryptococcus Neoformans Infection Using a Mouse Model of Pulmonary Cryptococcosis","volume":"4","author":"Wozniak","year":"2009","journal-title":"PloS One"},{"key":"B79","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-1-4939-8570-8_3","article-title":"Isolation and Characterization of Mononuclear Phagocytes in the Mouse Lung and Lymph Nodes","volume":"1809","author":"Gibbings","year":"2018","journal-title":"Methods Mol Biol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2161","article-title":"A Major Lung CD103 (Alphae)-Beta7 Integrin-Positive Epithelial Dendritic Cell Population Expressing Langerin and Tight Junction Proteins","volume":"176","author":"Sung","year":"2006","journal-title":"J Immunol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/srep00739","article-title":"Mechanisms of Dendritic Cell Lysosomal Killing of Cryptococcus","volume":"2","author":"Hole","year":"2012","journal-title":"Sci Rep"},{"key":"B82","doi-asserted-by":"publisher","first-page":"13619","DOI":"10.1038\/s41598-021-92991-6","article-title":"Antifungal Activity of Dendritic Cell Lysosomal Proteins Against Cryptococcus Neoformans","volume":"11","author":"Nelson","year":"2021","journal-title":"Sci Rep"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global Burden of Disease of HIV-Associated Cryptococcal Meningitis: An Updated Analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"B84","doi-asserted-by":"publisher","first-page":"e0233818","DOI":"10.1371\/journal.pone.0233818","article-title":"Intracellular Cryptococcus Neoformans Disrupts the Transcriptome Profile of M1- and M2-Polarized Host Macrophages","volume":"15","author":"Subramani","year":"2020","journal-title":"PloS One"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01046","article-title":"Distribution and Interaction of Murine Pulmonary Phagocytes in the Naive and Allergic Lung","volume":"9","author":"Hoffmann","year":"2018","journal-title":"Front Immunol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/imr.12223","article-title":"Macrophage Heterogeneity in Tissues: Phenotypic Diversity and Functions","volume":"262","author":"Gordon","year":"2014","journal-title":"Immunol Rev"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090326","article-title":"Monocyte-Mediated Defense Against Microbial Pathogens","volume":"26","author":"Serbina","year":"2008","journal-title":"Annu Rev Immunol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136221","article-title":"The State of Latency in Microbial Pathogenesis","volume":"130","author":"Pirofski","year":"2020","journal-title":"J Clin Invest"},{"key":"B89","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.celrep.2019.12.033","article-title":"Dual RNA-Seq of Mtb-Infected Macrophages In Vivo Reveals Ontologically Distinct Host-Pathogen Interactions","volume":"30","author":"Pisu","year":"2020","journal-title":"Cell Rep"},{"key":"B90","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3390\/jof4020049","article-title":"An Overview of Sex Bias in C. Neoformans Infections","volume":"4","author":"Guess","year":"2018","journal-title":"J Fungi (Basel)"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119964109","article-title":"Differential Ly-6C Expression Identifies the Recruited Macrophage Phenotype, Which Orchestrates the Regression of Murine Liver Fibrosis","volume":"109","author":"Ramachandran","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00405","article-title":"Transcriptomic Analysis of Monocyte-Derived Non-Phagocytic Macrophages Favors a Role in Limiting Tissue Repair and Fibrosis","volume":"11","author":"Butenko","year":"2020","journal-title":"Front Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090530","article-title":"Robust Th1 and Th17 Immunity Supports Pulmonary Clearance But Cannot Prevent Systemic Dissemination of Highly Virulent Cryptococcus Neoformans H99","volume":"175","author":"Zhang","year":"2009","journal-title":"Am J Pathol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.06.012","article-title":"Virulence Factors Identified by Cryptococcus Neoformans Mutant Screen Differentially Modulate Lung Immune Responses and Brain Dissemination","volume":"181","author":"He","year":"2012","journal-title":"Am J Pathol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1086\/593068","article-title":"A Gene-Dosage Effect for Interleukin-4 Receptor Alpha-Chain Expression has an Impact on Th2-Mediated Allergic Inflammation During Bronchopulmonary Mycosis","volume":"198","author":"Muller","year":"2008","journal-title":"J Infect Dis"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01738.x","article-title":"The MHC Class I Antigen Presentation Pathway: Strategies for Viral Immune Evasion","volume":"110","author":"Hewitt","year":"2003","journal-title":"Immunology"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.605958","article-title":"Reverse Signaling by MHC-I Molecules in Immune and Non-Immune Cell Types","volume":"11","author":"Muntjewerff","year":"2020","journal-title":"Front Immunol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01643","article-title":"Current Concepts of Antigen Cross-Presentation","volume":"9","author":"Embgenbroich","year":"2018","journal-title":"Front Immunol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055254","article-title":"The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules","volume":"35","author":"Cruz","year":"2017","journal-title":"Annu Rev Immunol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00292","article-title":"Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation","volume":"8","author":"Wieczorek","year":"2017","journal-title":"Front Immunol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00363","article-title":"Cross-Presentation of Cell-Associated Antigens by MHC Class I in Dendritic Cell Subsets","volume":"6","author":"Gutierrez-Martinez","year":"2015","journal-title":"Front Immunol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.1038\/s41467-019-10486-5","article-title":"Induction of Memory-Like Dendritic Cell Responses In Vivo","volume":"10","author":"Hole","year":"2019","journal-title":"Nat Commun"},{"key":"B103","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1177\/0300985811429314","article-title":"Immunological Variation Between Inbred Laboratory Mouse Strains: Points to Consider in Phenotyping Genetically Immunomodified Mice","volume":"49","author":"Sellers","year":"2012","journal-title":"Vet Pathol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0907","article-title":"CXCR3 Enhances a T-Cell-Dependent Epidermal Proliferative Response and Promotes Skin Tumorigenesis","volume":"71","author":"Winkler","year":"2011","journal-title":"Cancer Res"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702229104","article-title":"Disrupted Cardiac Development But Normal Hematopoiesis in Mice Deficient in the Second CXCL12\/SDF-1 Receptor, CXCR7","volume":"104","author":"Sierro","year":"2007","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.722500\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T05:13:54Z","timestamp":1632806034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.722500\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":105,"alternative-id":["10.3389\/fimmu.2021.722500"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.722500","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]},"article-number":"722500"}}