{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:49:03Z","timestamp":1774381743431,"version":"3.50.1"},"reference-count":108,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR S024611_1"],"award-info":[{"award-number":["MR S024611_1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Monocytes are considered to play a central role in the pathogenesis of Cryptococcus neoformans infection. Monocytes and monocyte-derived macrophages and dendritic cells are key components for the control of infection, but paradoxically they can also contribute to detrimental host responses and may even support fungal proliferation and dissemination. Simultaneously, the C. neoformans polysaccharide capsule can impair the functions of monocytes. Although monocytes are often seen as simple precursor cells, they also function as independent immune effector cells. In this review, we summarize these monocyte-specific functions during cryptococcal infection and the influence of C. neoformans on monocyte responses. We also cover the most recent findings on the functional and phenotypic heterogeneity of monocytes and discuss how new advanced technologies provide a platform to address outstanding questions in the field.<\/jats:p>","DOI":"10.3390\/jof6030111","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T10:54:46Z","timestamp":1594896886000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Diverse Roles of Monocytes in Cryptococcosis"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5376-7243","authenticated-orcid":false,"given":"Man Shun","family":"Fu","sequence":"first","affiliation":[{"name":"Institute of Immunology & Immunotherapy, Institute of Microbiology & Infection, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5424-7074","authenticated-orcid":false,"given":"Rebecca A.","family":"Drummond","sequence":"additional","affiliation":[{"name":"Institute of Immunology & Immunotherapy, Institute of Microbiology & Infection, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/cyto.a.20859","article-title":"Evaluation of a 12-color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans","volume":"77","author":"Autissier","year":"2010","journal-title":"Cytom. Part A"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cellimm.2014.05.010","article-title":"Monocyte homeostasis and the plasticity of inflammatory monocytes","volume":"291","author":"Mitchell","year":"2014","journal-title":"Cell. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1146\/annurev-immunol-032414-112220","article-title":"Macrophages: Development and Tissue Specialization","volume":"33","author":"Varol","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.it.2013.06.001","article-title":"Inflammatory dendritic cells in mice and humans","volume":"34","author":"Segura","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/B978-0-12-417028-5.00003-X","article-title":"Chapter Three\u2014A Close Encounter of the Third Kind: Monocyte-Derived Cells","volume":"120","author":"Murphy","year":"2013","journal-title":"Advances in Immunology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12026-012-8297-3","article-title":"The three human monocyte subsets: Implications for health and disease","volume":"53","author":"Wong","year":"2012","journal-title":"Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S2213-2600(18)30508-3","article-title":"Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: A retrospective, multicentre cohort study","volume":"7","author":"Scott","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5859","DOI":"10.2174\/1381612811319330004","article-title":"Novel monocyte biomarkers of atherogenic conditions","volume":"19","author":"Gratchev","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/imm.12371","article-title":"Microarray analysis of Mycobacterium tuberculosis-infected monocytes reveals IL26 as a new candidate gene for tuberculosis susceptibility","volume":"144","year":"2015","journal-title":"Immunology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.chom.2009.10.007","article-title":"Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection","volume":"6","author":"Hohl","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Espinosa, V., Jhingran, A., Dutta, O., Kasahara, S., Donnelly, R., Du, P., Rosenfeld, J., Leiner, I., Chen, C.C., and Ron, Y. (2014). Inflammatory Monocytes Orchestrate Innate Antifungal Immunity in the Lung. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003940"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/infdis\/jit413","article-title":"Inflammatory Monocytes Mediate Early and Organ-Specific Innate Defense During Systemic Candidiasis","volume":"209","author":"Ngo","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.immuni.2017.05.009","article-title":"Inflammatory Ly6Chigh Monocytes Protect against Candidiasis through IL-15-Driven NK Cell\/Neutrophil Activation","volume":"46","year":"2017","journal-title":"Immunity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.4049\/jimmunol.0901316","article-title":"The CCL7-CCL2-CCR2 Axis Regulates IL-4 Production in Lungs and Fungal Immunity","volume":"183","author":"Szymczak","year":"2009","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2021","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":"ref_17","doi-asserted-by":"crossref","first-page":"932","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":"ref_18","doi-asserted-by":"crossref","first-page":"610","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":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1099\/jmm.0.003293-0","article-title":"Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus","volume":"58","author":"Loeffler","year":"2009","journal-title":"J. Med. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rajasingham, R., Smith, R.M., Park, B.J., Jarvis, J.N., Govender, N.P., Chiller, T.M., Denning, D.W., Loyse, A., and Boulware, D.R. (2017). Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis. Lancet Infect. Dis.","DOI":"10.1016\/S1473-3099(17)30243-8"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1128\/jb.62.6.685-690.1951","article-title":"Isolation of cryptococcus neoformans from soil","volume":"62","author":"Emmons","year":"1951","journal-title":"J. Bacteriol."},{"key":"ref_22","first-page":"227","article-title":"Saprophytic sources of Cryptococcus neoformans associated with the pigeon (Columba livia)","volume":"62","author":"Emmons","year":"1955","journal-title":"Am. J. Hyg."},{"key":"ref_23","first-page":"97","article-title":"First isolation of Cryptococcus neoformans genotype VNI MAT-alpha from wood inside hollow trunks of Hymenaea courbaril","volume":"54","author":"Santos","year":"2016","journal-title":"Med. Mycol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.4049\/jimmunol.175.5.3244","article-title":"An Innate Immune System Cell Is a Major Determinant of Species-Related Susceptibility Differences to Fungal Pneumonia","volume":"175","author":"Shao","year":"2005","journal-title":"J. Immunol."},{"key":"ref_25","first-page":"1122","article-title":"Long-term Mortality and Disability in Cryptococcal Meningitis: A Systematic Literature Review","volume":"66","author":"Pasquier","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Beardsley, J., Sorrell, T.C., and Chen, S.C.A. (2019). Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients. J. Fungi, 5.","DOI":"10.3390\/jof5030071"},{"key":"ref_27","doi-asserted-by":"crossref","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":"ref_28","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1084\/jem.194.9.1361","article-title":"Inflammatory Chemokine Transport and Presentation in HEV A Remote Control Mechanism for Monocyte Recruitment to Lymph Nodes in Inflamed Tissues","volume":"194","author":"Palframan","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.4049\/jimmunol.162.3.1618","article-title":"Specific activated T cells regulate IL-12 production by human monocytes stimulated with Cryptococcus neoformans","volume":"162","author":"Retini","year":"1999","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1002\/(SICI)1521-4141(200005)30:5<1385::AID-IMMU1385>3.0.CO;2-K","article-title":"T lymphocyte and monocyte interaction by CD40\/CD40 ligand facilitates a lymphoproliferative response and killing of Cryptococcus neoformans in vitro","volume":"30","author":"Vecchiarelli","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"120","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":"ref_32","doi-asserted-by":"crossref","unstructured":"Heung, L.J., and Hohl, T.M. (2019). Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007627"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4225","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":"ref_34","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1086\/341564","article-title":"Pathogenesis of Cerebral Cryptococcus neoformans Infection after Fungemia","volume":"186","author":"Lortholary","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4792","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":"ref_36","doi-asserted-by":"crossref","unstructured":"Santiago-Tirado, F.H., Onken, M.D., Cooper, J.A., Klein, R.S., and Doering, T.L. (2017). Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen. mBio, 8.","DOI":"10.1128\/mBio.02183-16"},{"key":"ref_37","doi-asserted-by":"crossref","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":"ref_38","doi-asserted-by":"crossref","unstructured":"Sun, D., Zhang, M., Sun, P., Liu, G., Strickland, A.B., Chen, Y., Fu, Y., Yosri, M., and Shi, M. (2020). VCAM1\/VLA4 interaction mediates Ly6Clow monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008361"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Alvarez, M., Burn, T., Luo, Y., Pirofski, L., and Casadevall, A. (2009). The outcome of Cryptococcus neoformansintracellular pathogenesis in human monocytes. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-51"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.4049\/jimmunol.166.7.4620","article-title":"Toll-Like Receptor 4 Mediates Intracellular Signaling Without TNF-\u03b1 Release in Response to Cryptococcus neoformans Polysaccharide Capsule","volume":"166","author":"Shoham","year":"2001","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6064","DOI":"10.1128\/IAI.69.10.6064-6073.2001","article-title":"Interdependency of Interleukin-10 and Interleukin-12 in Regulation of T-Cell Differentiation and Effector Function of Monocytes in Response to Stimulation with Cryptococcus neoformans","volume":"69","author":"Retini","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1128\/IAI.68.2.558-563.2000","article-title":"Early induction of interleukin-12 by human monocytes exposed to Cryptococcus neoformans mannoproteins","volume":"68","author":"Pitzurra","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<114::AID-IMMU114>3.0.CO;2-B","article-title":"Cryptococcus neoformans differently regulates B7-1 (CD80) and B7-2 (CD86) expression on human monocytes","volume":"28","author":"Vecchiarelli","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1086\/314458","article-title":"Cryptococcus neoformans and Candida albicans regulate CD4 expression on human monocytes","volume":"178","author":"Pietrella","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1128\/iai.65.6.2454-2456.1997","article-title":"Interleukin-6 production by human monocytes stimulated with Cryptococcus neoformans components","volume":"65","author":"Delfino","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Masso-Silva, J., Espinosa, V., Liu, T.B., Wang, Y., Xue, C., and Rivera, A. (2018). The F-Box Protein Fbp1 Shapes the Immunogenic Potential of Cryptococcus neoformans. mBio, 9.","DOI":"10.1128\/mBio.01828-17"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1080\/21505594.2017.1385692","article-title":"IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote clearance of Cryptococcus neoformans infection in a mouse model","volume":"8","author":"Li","year":"2017","journal-title":"Virulence"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1182\/blood.V74.7.2527.2527","article-title":"Identification and characterization of a novel monocyte subpopulation in human peripheral blood","volume":"74","author":"Passlick","year":"1989","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0167-5699(93)90212-4","article-title":"CD14: Cell surface receptor and differentiation marker","volume":"14","author":"Ulevitch","year":"1993","journal-title":"Immunol. Today"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1182\/blood-2010-02-258558","article-title":"Nomenclature of monocytes and dendritic cells in blood","volume":"116","author":"Ancuta","year":"2010","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.immuni.2013.08.007","article-title":"Minimal Differentiation of Classical Monocytes as They Survey Steady-State Tissues and Transport Antigen to Lymph Nodes","volume":"39","author":"Jakubzick","year":"2013","journal-title":"Immunity"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1084\/jem.20170355","article-title":"The fate and lifespan of human monocyte subsets in steady state and systemic inflammation","volume":"214","author":"Patel","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.immuni.2012.12.001","article-title":"Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis","volume":"38","author":"Yona","year":"2013","journal-title":"Immunity"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Orekhov, A.N., Orekhova, V.A., Nikiforov, N.G., Myasoedova, V.A., Grechko, A.V., Romanenko, E.B., Zhang, D., and Chistiakov, D.A. (2019). Monocyte differentiation and macrophage polarization. Vessel Plus, 2019.","DOI":"10.20517\/2574-1209.2019.04"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6346","DOI":"10.4049\/jimmunol.174.10.6346","article-title":"Role of IFN-gamma in regulating T2 immunity and the development of alternatively activated macrophages during allergic bronchopulmonary mycosis","volume":"174","author":"Arora","year":"2005","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"774","DOI":"10.2353\/ajpath.2010.090634","article-title":"Pulmonary Infection with an Interferon-\u03b3-Producing Cryptococcus neoformans Strain Results in Classical Macrophage Activation and Protection","volume":"176","author":"Hardison","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0006-291X(88)80015-9","article-title":"Nitric oxide: A cytotoxic activated macrophage effector molecule","volume":"157","author":"Hibbs","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1165\/ajrcmb.20.3.3252","article-title":"IFN-gamma potentiates the release of TNF-alpha and MIP-1alpha by alveolar macrophages during allergic reactions","volume":"20","author":"Bissonnette","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1161\/ATVBAHA.114.304650","article-title":"Nonclassical Patrolling Monocyte Function in the Vasculature","volume":"35","author":"Thomas","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1128\/MCB.20.11.4106-4114.2000","article-title":"Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion","volume":"20","author":"Jung","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0163-4453(97)93042-5","article-title":"Monocyte dysfunction in patients with acquired immunodeficiency syndrome (AIDS) versus Cryptococcus neoformans","volume":"35","author":"Monari","year":"1997","journal-title":"J. Infect."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/infdis\/jiw007","article-title":"A Glucuronoxylomannan-Associated Immune Signature, Characterized by Monocyte Deactivation and an Increased Interleukin 10 Level, Is a Predictor of Death in Cryptococcal Meningitis","volume":"213","author":"Scriven","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jinf.2006.03.018","article-title":"Functional defect of natural immune system in an apparent immunocompetent patient with pulmonary cryptococcosis","volume":"54","author":"Marroni","year":"2007","journal-title":"J. Infect."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Panackal, A.A., Wuest, S.C., Lin, Y.C., Wu, T., Zhang, N., Kosa, P., Komori, M., Blake, A., Browne, S.K., and Rosen, L.B. (2015). Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004884"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Meya, D.B., Okurut, S., Zziwa, G., Cose, S., Bohjanen, P.R., Mayanja-Kizza, H., Joloba, M., Boulware, D.R., Yukari Manabe, C., and Wahl, S. (2017). Monocyte Phenotype and IFN-\u03b3-Inducible Cytokine Responses Are Associated with Cryptococcal Immune Reconstitution Inflammatory Syndrome. J. Fungi, 3.","DOI":"10.3390\/jof3020028"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0171-2985(11)80187-7","article-title":"Monoclonal antibody EBM11 (anti-CD68) discriminates between dendritic cells and macrophages after short-term culture","volume":"183","author":"Betjes","year":"1991","journal-title":"Immunobiology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2050-7771-2-1","article-title":"Monocyte and macrophage differentiation: Circulation inflammatory monocyte as biomarker for inflammatory diseases","volume":"2","author":"Yang","year":"2014","journal-title":"Biomark. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.4049\/jimmunol.168.9.4659","article-title":"Differential Roles of CC Chemokine Ligand 2\/Monocyte Chemotactic Protein-1 and CCR2 in the Development of T1 Immunity","volume":"168","author":"Traynor","year":"2002","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1128\/IAI.01270-10","article-title":"Effect of cytokine interplay on macrophage polarization during chronic pulmonary infection with Cryptococcus neoformans","volume":"79","author":"Arora","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5367","DOI":"10.4049\/jimmunol.179.8.5367","article-title":"IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans","volume":"179","author":"Stenzel","year":"2007","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0008-6215(97)10058-1","article-title":"Structural characterization of the galactoxylomannan of Cryptococcus neoformans Cap67","volume":"306","author":"Vaishnav","year":"1998","journal-title":"Carbohydr. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1074\/jbc.M509465200","article-title":"The physical properties of the capsular polysaccharides from Cryptococcus neoformans suggest features for capsule construction","volume":"281","author":"McFadden","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s12038-014-9496-y","article-title":"Lack of IL-6 increases blood-brain barrier permeability in fungal meningitis","volume":"40","author":"Li","year":"2015","journal-title":"J. Biosci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Netea, M.G., Joosten, L.A.B., Latz, E., Mills, K.H.G., Natoli, G., Stunnenberg, H.G., O\u2019Neill, L.A.J., and Xavier, R.J. (2016). Trained immunity: A program of innate immune memory in health and disease. Science, 352.","DOI":"10.1126\/science.aaf1098"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.chom.2011.04.006","article-title":"Trained Immunity: A Memory for Innate Host Defense","volume":"9","author":"Netea","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.chom.2012.06.006","article-title":"Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes","volume":"12","author":"Quintin","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Saeed, S., Quintin, J., Kerstens, H.H.D., Rao, N.A., Aghajanirefah, A., Matarese, F., Cheng, S.C., Ratter, J., Berentsen, K., and van der Ent, M.A. (2014). Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science, 345.","DOI":"10.1126\/science.1251086"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1128\/iai.20.3.804-810.1978","article-title":"Protective effect of glucan against systemic Staphylococcus aureus septicemia in normal and leukemic mice","volume":"20","author":"Luzio","year":"1978","journal-title":"Infect. Immun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.micinf.2013.03.002","article-title":"Dectin-1 plays a redundant role in the immunomodulatory activities of \u03b2-glucan-rich ligands in vivo","volume":"15","author":"Marakalala","year":"2013","journal-title":"Microbes Infect."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7961","DOI":"10.1074\/jbc.M115.699645","article-title":"Fungal Chitin Induces Trained Immunity in Human Monocytes during Cross-talk of the Host with Saccharomyces cerevisiae","volume":"291","author":"Rizzetto","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/j.1348-0421.1984.tb00746.x","article-title":"Protecting Effect of Chitin and Chitosan on Experimentally Induced Murine Candidiasis","volume":"28","author":"Suzuki","year":"1984","journal-title":"Microbiol. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1111\/j.1348-0421.1986.tb03026.x","article-title":"Protective Effect of Acidic Mannan Fraction of Bakers\u2019 Yeast on Experimental Candidiasis in Mice","volume":"30","author":"Okawa","year":"1986","journal-title":"Microbiol. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cell.2017.11.034","article-title":"Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity","volume":"172","author":"Mitroulis","year":"2018","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"E66","DOI":"10.1542\/peds.107.5.e66","article-title":"Serologic evidence for Cryptococcus neoformans infection in early childhood","volume":"107","author":"Goldman","year":"2001","journal-title":"Pediatrics"},{"key":"ref_85","doi-asserted-by":"crossref","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":"ref_86","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41593-020-0618-6","article-title":"Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury","volume":"23","author":"Ydens","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1039\/b202306g","article-title":"Simultaneous determination of proteins using an element-tagged immunoassay coupled with ICP-MS detection","volume":"17","author":"Quinn","year":"2002","journal-title":"J. Anal. At. Spectrom."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1039\/B201494G","article-title":"The potential for elemental analysis in biotechnology","volume":"17","author":"Baranov","year":"2002","journal-title":"J. Anal. At. Spectrom."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jim.2005.09.020","article-title":"Multiple cellular antigen detection by ICP-MS","volume":"308","author":"Ornatsky","year":"2006","journal-title":"J. Immunol. Methods"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6111","DOI":"10.1002\/anie.200700796","article-title":"Polymer-Based Elemental Tags for Sensitive Bioassays","volume":"46","author":"Lou","year":"2007","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jim.2010.07.002","article-title":"Highly multiparametric analysis by mass cytometry","volume":"361","author":"Ornatsky","year":"2010","journal-title":"J. Immunol. Methods"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1161\/ATVBAHA.117.309145","article-title":"Human blood monocyte subsets: A new gating strategy defined using cell surface markers identified by mass cytometry","volume":"37","author":"Thomas","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1055\/s-0039-1700871","article-title":"High-Content Immunophenotyping and Hierarchical Clustering Reveal Sources of Heterogeneity and New Surface Markers of Human Blood Monocyte Subsets","volume":"120","author":"Hoffmann","year":"2020","journal-title":"Thromb. Haemost."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41590-020-0661-1","article-title":"Cxcl10+ monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation","volume":"21","author":"Giladi","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/13693780410001731510","article-title":"Cytokine and chemokine expression in the central nervous system associated with protective cell-mediated immunity against Cryptococcus neoformans","volume":"43","author":"Uicker","year":"2005","journal-title":"Med. Mycol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.ajpath.2018.03.015","article-title":"The Early Innate Immune Response to, and Phagocyte-Dependent Entry of, Cryptococcus neoformans Map to the Perivascular Space of Cortical Post-Capillary Venules in Neurocryptococcosis","volume":"188","author":"Djordjevic","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1093\/infdis\/jit388","article-title":"Chemokine levels and chemokine receptor expression in the blood and the cerebrospinal fluid of HIV-infected patients with cryptococcal meningitis and cryptococcosis-associated immune reconstitution inflammatory syndrome","volume":"208","author":"Chang","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Neal, L.M., Xing, E., Xu, J., Kolbe, J.L., Osterholzer, J.J., Segal, B.M., Williamson, P.R., and Olszewski, M.A. (2017). CD4+ T Cells Orchestrate Lethal Immune Pathology despite Fungal Clearance during Cryptococcus neoformans Meningoencephalitis. mBio, 8.","DOI":"10.1128\/mBio.01415-17"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"125","DOI":"10.21037\/atm.2020.02.35","article-title":"Single-cell transcriptomics reveals the alteration of peripheral blood mononuclear cells driven by sepsis","volume":"8","author":"Wen","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Shnayder, M., Nachshon, A., Rozman, B., Bernshtein, B., Lavi, M., Fein, N., Poole, E., Avdic, S., Blyth, E., and Gottlieb, D. (2020). Single cell analysis reveals human cytomegalovirus drives latently infected cells towards an anergic-like monocyte state. Elife, 9.","DOI":"10.7554\/eLife.52168"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"12597","DOI":"10.1038\/ncomms12597","article-title":"Regulation of monocyte cell fate by blood vessels mediated by Notch signalling","volume":"7","author":"Gamrekelashvili","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/ni.2063","article-title":"The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and survival of Ly6C\u2212 monocytes","volume":"12","author":"Hanna","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.immuni.2017.10.021","article-title":"Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes","volume":"47","author":"Coetzee","year":"2017","journal-title":"Immunity"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Y\u00e1\u00f1ez, A., Meg\u00edas, J., O\u2019Connor, J.E., Gozalbo, D., and Gil, M.L. (2011). Candida albicans induces selective development of macrophages and monocyte derived dendritic cells by a TLR2 dependent signalling. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024761"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.immuni.2015.05.011","article-title":"Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection","volume":"42","author":"Askenase","year":"2015","journal-title":"Immunity"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1462-5822.2009.01382.x","article-title":"Signalling through TLR2\/MyD88 induces differentiation of murine bone marrow stem and progenitor cells to functional phagocytes in response to Candida albicans","volume":"12","author":"Flores","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S1470-2045(16)00078-4","article-title":"Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: A single-centre, open-label, dose-finding, non-randomised, phase 1b trial","volume":"17","author":"Nywening","year":"2016","journal-title":"Lancet Oncol."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/6\/3\/111\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:03Z","timestamp":1760176143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/6\/3\/111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,16]]},"references-count":108,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["jof6030111"],"URL":"https:\/\/doi.org\/10.3390\/jof6030111","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,16]]}}}