{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:40:33Z","timestamp":1790710833460,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T00:00:00Z","timestamp":1505347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T00:00:00Z","timestamp":1505347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To study interactions of airborne pathogens, e.g. <jats:italic>Aspergillus<\/jats:italic> (<jats:italic>A.) fumigatus<\/jats:italic> with upper and lower respiratory tract epithelial and immune cells, we set up a perfused 3D human bronchial and small airway epithelial cell system. Culturing of normal human bronchial or small airway epithelial (NHBE, SAE) cells under air liquid interphase (ALI) and perfusion resulted in a significantly accelerated development of the lung epithelia associated with higher ciliogenesis, cilia movement, mucus-production and improved barrier function compared to growth under static conditions. Following the accelerated differentiation under perfusion, epithelial cells were transferred into static conditions and antigen-presenting cells (APCs) added to study their functionality upon infection with <jats:italic>A. fumigatus<\/jats:italic>. Fungi were efficiently sensed by apically applied macrophages or basolaterally adhered dendritic cells (DCs), as illustrated by phagocytosis, maturation and migration characteristics. We illustrate here that perfusion greatly improves differentiation of primary epithelial cells <jats:italic>in vitro<\/jats:italic>, which enables fast-track addition of primary immune cells and significant shortening of experimental procedures. Additionally, co-cultured primary DCs and macrophages were fully functional and fulfilled their tasks of sensing and sampling fungal pathogens present at the apical surface of epithelial cells, thereby promoting novel possibilities to study airborne infections under conditions mimicking the <jats:italic>in vivo<\/jats:italic> situation.<\/jats:p>","DOI":"10.1038\/s41598-017-11271-4","type":"journal-article","created":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T11:01:35Z","timestamp":1505127695000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Fast-track development of an in vitro 3D lung\/immune cell model to study Aspergillus infections"],"prefix":"10.1038","volume":"7","author":[{"given":"P.","family":"Chandorkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-7654","authenticated-orcid":false,"given":"W.","family":"Posch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Zaderer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Blatzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Steger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. G.","family":"Ammann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"H\u00f6rtnagl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Lass-Fl\u00f6rl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-5118","authenticated-orcid":false,"given":"D.","family":"Wilflingseder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,14]]},"reference":[{"key":"11271_CR1","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/ncb3510","volume":"19","author":"YW Chen","year":"2017","unstructured":"Chen, Y. W. et al. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol \n                           19, 542\u2013549, doi:10.1038\/ncb3510 (2017).","journal-title":"Nat Cell Biol"},{"key":"11271_CR2","doi-asserted-by":"publisher","unstructured":"Bucchieri, F. et al. Functional characterization of a novel 3D model of the epithelial-mesenchymal trophic unit. Exp Lung Res, 1\u201311, doi:10.1080\/01902148.2017.1303098 (2017).","DOI":"10.1080\/01902148.2017.1303098"},{"key":"11271_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-016-0178-9","volume":"13","author":"I Tomasek","year":"2016","unstructured":"Tomasek, I. et al. Combined exposure of diesel exhaust particles and respirable Soufriere Hills volcanic ash causes a (pro-)inflammatory response in an in vitro multicellular epithelial tissue barrier model. Part Fibre Toxicol \n                           13, 67, doi:10.1186\/s12989-016-0178-9 (2016).","journal-title":"Part Fibre Toxicol"},{"key":"11271_CR4","doi-asserted-by":"publisher","first-page":"282","DOI":"10.4168\/aair.2016.8.4.282","volume":"8","author":"A Shah","year":"2016","unstructured":"Shah, A. & Panjabi, C. Allergic Bronchopulmonary Aspergillosis: A Perplexing Clinical Entity. Allergy Asthma Immunol Res \n                           8, 282\u2013297 (2016).","journal-title":"Allergy Asthma Immunol Res"},{"key":"11271_CR5","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1056\/NEJM199707243370407","volume":"337","author":"RD deShazo","year":"1997","unstructured":"deShazo, R. D., Chapin, K. & Swain, R. E. Fungal sinusitis. The New England journal of medicine \n                           337, 254\u2013259, doi:10.1056\/nejm199707243370407 (1997).","journal-title":"The New England journal of medicine"},{"key":"11271_CR6","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0092-8674(00)80412-2","volume":"91","author":"R Medzhitov","year":"1997","unstructured":"Medzhitov, R. & Janeway Jr, C. A. Innate Immunity: The Virtues of a Nonclonal System of Recognition. Cell \n                           91, 295\u2013298, doi:10.1016\/S0092-8674(00)80412-2 (1997).","journal-title":"Cell"},{"key":"11271_CR7","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nri2939","volume":"11","author":"L Romani","year":"2011","unstructured":"Romani, L. Immunity to fungal infections. Nat Rev Immunol \n                           11, 275\u2013288 (2011).","journal-title":"Nat Rev Immunol"},{"key":"11271_CR8","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/myc.12052","volume":"56","author":"C Lass-Fl\u00f6rl","year":"2013","unstructured":"Lass-Fl\u00f6rl, C., Roilides, E., L\u00f6ffler, J., Wilflingseder, D. & Romani, L. Minireview: host defence in invasive aspergillosis. Mycoses \n                           56, 403\u2013413, doi:10.1111\/myc.12052 (2013).","journal-title":"Mycoses"},{"key":"11271_CR9","first-page":"S203","volume":"41","author":"MR B","year":"2005","unstructured":"B, M. R. Pathophysiology and immunology of allergic bronchopulmonary aspergillosis. Medical Mycology \n                           41, S203\u2013206 (2005).","journal-title":"Medical Mycology"},{"key":"11271_CR10","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1128\/EC.00274-07","volume":"6","author":"TM Hohl","year":"2007","unstructured":"Hohl, T. M. & Feldmesser, M. Aspergillus fumigatus: Principles of Pathogenesis and Host Defense. Eukaryotic Cell \n                           6, 1953\u20131963, doi:10.1128\/EC.00274-07 (2007).","journal-title":"Eukaryotic Cell"},{"key":"11271_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041897","volume":"7","author":"L Bozzacco","year":"2012","unstructured":"Bozzacco, L. et al. Strategy for identifying dendritic cell-processed CD4+ T cell epitopes from the HIV gag p24 protein. PLoS One \n                           7, e41897, doi:10.1371\/journal.pone.0041897 (2012).","journal-title":"PLoS One"},{"key":"11271_CR12","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.1073\/pnas.0711976105","volume":"105","author":"C Trumpfheller","year":"2008","unstructured":"Trumpfheller, C. et al. The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci USA \n                           105, 2574\u20132579, doi:10.1073\/pnas.0711976105 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"11271_CR13","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1084\/jem.20052005","volume":"203","author":"C Trumpfheller","year":"2006","unstructured":"Trumpfheller, C. et al. Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. J Exp Med \n                           203, 607\u2013617, doi:10.1084\/jem.20052005 (2006).","journal-title":"J Exp Med"},{"key":"11271_CR14","doi-asserted-by":"publisher","first-page":"5940","DOI":"10.4049\/jimmunol.171.11.5940","volume":"171","author":"RS Goldszmid","year":"2003","unstructured":"Goldszmid, R. S. et al. Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma. J Immunol \n                           171, 5940\u20135947 (2003).","journal-title":"J Immunol"},{"key":"11271_CR15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.0105-2896.2009.00888.x","volume":"234","author":"RM Steinman","year":"2010","unstructured":"Steinman, R. M. & Idoyaga, J. Features of the dendritic cell lineage. Immunol Rev \n                           234, 5\u201317, doi:10.1111\/j.0105-2896.2009.00888.x (2010).","journal-title":"Immunol Rev"},{"key":"11271_CR16","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/693023","volume":"2013","author":"H Sales-Campos","year":"2013","unstructured":"Sales-Campos, H., Tonani, L., Cardoso, C. R. B. & Kress, M. R. V. Z. The Immune Interplay between the Host and the Pathogen in Aspergillus fumigatus Lung Infection. BioMed Research International \n                           2013, 693023, doi:10.1155\/2013\/693023 (2013).","journal-title":"BioMed Research International"},{"key":"11271_CR17","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1002\/eji.201344404","volume":"44","author":"E Kolwijck","year":"2014","unstructured":"Kolwijck, E. & van de Veerdonk, F. L. The potential impact of the pulmonary microbiome on immunopathogenesis of Aspergillus-related lung disease. European Journal of Immunology \n                           44, 3156\u20133165, doi:10.1002\/eji.201344404 (2014).","journal-title":"European Journal of Immunology"},{"key":"11271_CR18","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1007\/s00134-007-0792-y","volume":"33","author":"W Meersseman","year":"2007","unstructured":"Meersseman, W. & Van Wijngaerden, E. Invasive aspergillosis in the ICU: an emerging disease. Intensive Care Medicine \n                           33, 1679\u20131681, doi:10.1007\/s00134-007-0792-y (2007).","journal-title":"Intensive Care Medicine"},{"key":"11271_CR19","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1007\/s00134-012-2673-2","volume":"38","author":"J Wauters","year":"2012","unstructured":"Wauters, J. et al. Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study. Intensive Care Medicine \n                           38, 1761\u20131768, doi:10.1007\/s00134-012-2673-2 (2012).","journal-title":"Intensive Care Medicine"},{"key":"11271_CR20","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1111\/cea.12141","volume":"43","author":"R Agarwal","year":"2013","unstructured":"Agarwal, R. et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clinical & Experimental Allergy \n                           43, 850\u2013873, doi:10.1111\/cea.12141 (2013).","journal-title":"Clinical & Experimental Allergy"},{"key":"11271_CR21","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1046\/j.1440-1711.1999.00877.x","volume":"77","author":"CR Parish","year":"1999","unstructured":"Parish, C. R. Fluorescent dyes for lymphocyte migration and proliferation studies. Immunol Cell Biol \n                           77, 499\u2013508, doi:10.1046\/j.1440-1711.1999.00877.x (1999).","journal-title":"Immunol Cell Biol"},{"key":"11271_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-10-31","volume":"10","author":"SG Klein","year":"2013","unstructured":"Klein, S. G., Serchi, T., Hoffmann, L., Blomeke, B. & Gutleb, A. C. An improved 3D tetraculture system mimicking the cellular organisation at the alveolar barrier to study the potential toxic effects of particles on the lung. Part Fibre Toxicol \n                           10, 31, doi:10.1186\/1743-8977-10-31 (2013).","journal-title":"Part Fibre Toxicol"},{"key":"11271_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1165\/rcmb.2013-0390TE","volume":"51","author":"P Ding","year":"2014","unstructured":"Ding, P., Wu, H., Fang, L., Wu, M. & Liu, R. Transmigration and Phagocytosis of Macrophages in an Airway Infection Model Using Four-dimensional Techniques. American Journal of Respiratory Cell and Molecular Biology \n                           51, 1\u201310, doi:10.1165\/rcmb.2013-0390TE (2014).","journal-title":"American Journal of Respiratory Cell and Molecular Biology"},{"key":"11271_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1743-8977-10-31","volume":"10","author":"SG Klein","year":"2013","unstructured":"Klein, S. G., Serchi, T., Hoffmann, L., Bl\u00f6meke, B. & Gutleb, A. C. An improved 3D tetraculture system mimicking the cellular organisation at the alveolar barrier to study the potential toxic effects of particles on the lung. Particle and Fibre Toxicology \n                           10, 1\u201318, doi:10.1186\/1743-8977-10-31 (2013).","journal-title":"Particle and Fibre Toxicology"},{"key":"11271_CR25","doi-asserted-by":"publisher","unstructured":"Schwarz, J. et al. Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal-to-Noise Ratio and Dependent on GRK6. Curr Biol, doi:10.1016\/j.cub.2017.04.004 (2017).","DOI":"10.1016\/j.cub.2017.04.004"},{"key":"11271_CR26","doi-asserted-by":"publisher","first-page":"R24","DOI":"10.1016\/j.cub.2016.11.035","volume":"27","author":"J Muller","year":"2017","unstructured":"Muller, J. & Sixt, M. Cell Migration: Making the Waves. Curr Biol \n                           27, R24\u2013R25, doi:10.1016\/j.cub.2016.11.035 (2017).","journal-title":"Curr Biol"},{"key":"11271_CR27","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/1465-9921-11-162","volume":"11","author":"SR Franzd\u00f3ttir","year":"2010","unstructured":"Franzd\u00f3ttir, S. R. et al. Airway branching morphogenesis in three dimensional culture. Respiratory Research \n                           11, 162\u2013162, doi:10.1186\/1465-9921-11-162 (2010).","journal-title":"Respiratory Research"},{"key":"11271_CR28","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nmeth1015","volume":"4","author":"GY Lee","year":"2007","unstructured":"Lee, G. Y., Kenny, P. A., Lee, E. H. & Bissell, M. J. Three-dimensional culture models of normal and malignant breast epithelial cells. Nature methods \n                           4, 359\u2013365, doi:10.1038\/nmeth1015 (2007).","journal-title":"Nature methods"},{"key":"11271_CR29","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.tiv.2012.10.007","volume":"27","author":"UG Sauer","year":"2013","unstructured":"Sauer, U. G. et al. In vivo-in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems. Toxicol In Vitro \n                           27, 174\u2013190, doi:10.1016\/j.tiv.2012.10.007 (2013).","journal-title":"Toxicol In Vitro"},{"key":"11271_CR30","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1183\/09031936.00044008","volume":"32","author":"E Alfaro-Moreno","year":"2008","unstructured":"Alfaro-Moreno, E. et al. Co-cultures of multiple cell types mimic pulmonary cell communication in response to urban PM10. Eur Respir J \n                           32, 1184\u20131194, doi:10.1183\/09031936.00044008 (2008).","journal-title":"Eur Respir J"},{"key":"11271_CR31","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1016\/j.tiv.2011.06.019","volume":"25","author":"DJ Cooney","year":"2011","unstructured":"Cooney, D. J. & Hickey, A. J. Cellular response to the deposition of diesel exhaust particle aerosols onto human lung cells grown at the air\u2013liquid interface by inertial impaction. Toxicology in Vitro \n                           25, 1953\u20131965, doi:10.1016\/j.tiv.2011.06.019 (2011).","journal-title":"Toxicology in Vitro"},{"key":"11271_CR32","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.3762\/bjnano.5.171","volume":"5","author":"A Panas","year":"2014","unstructured":"Panas, A. et al. Silica nanoparticles are less toxic to human lung cells when deposited at the air\u2013liquid interface compared to conventional submerged exposure. Beilstein Journal of Nanotechnology \n                           5, 1590\u20131602, doi:10.3762\/bjnano.5.171 (2014).","journal-title":"Beilstein Journal of Nanotechnology"},{"key":"11271_CR33","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1128\/IAI.73.2.1129-1140.2005","volume":"73","author":"AJ Carterson","year":"2005","unstructured":"Carterson, A. J. et al. A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis. Infect Immun \n                           73, 1129\u20131140, doi:10.1128\/iai.73.2.1129-1140.2005 (2005).","journal-title":"Infect Immun"},{"key":"11271_CR34","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.0105-2896.2009.00888.x","volume":"234","author":"RM Steinman","year":"2010","unstructured":"Steinman, R. M. & Idoyaga, J. Features of the dendritic cell lineage. Immunological Reviews \n                           234, 5\u201317, doi:10.1111\/j.0105-2896.2009.00888.x (2010).","journal-title":"Immunological Reviews"},{"key":"11271_CR35","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1038\/cr.2010.94","volume":"20","author":"AC Soloff","year":"2010","unstructured":"Soloff, A. C. & Barratt-Boyes, S. M. Enemy at the gates: dendritic cells and immunity to mucosal pathogens. Cell Res \n                           20, 872\u2013885 (2010).","journal-title":"Cell Res"},{"key":"11271_CR36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003940","volume":"10","author":"V Espinosa","year":"2014","unstructured":"Espinosa, V. et al. Inflammatory Monocytes Orchestrate Innate Antifungal Immunity in the Lung. PLoS Pathogens \n                           10, e1003940, doi:10.1371\/journal.ppat.1003940 (2014).","journal-title":"PLoS Pathogens"},{"key":"11271_CR37","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.4049\/jimmunol.178.4.2000","volume":"178","author":"L Landsman","year":"2007","unstructured":"Landsman, L., Varol, C. & Jung, S. Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung. The Journal of Immunology \n                           178, 2000\u20132007, doi:10.4049\/jimmunol.178.4.2000 (2007).","journal-title":"The Journal of Immunology"},{"key":"11271_CR38","doi-asserted-by":"publisher","first-page":"8044","DOI":"10.4049\/jimmunol.0902823","volume":"183","author":"JJ Osterholzer","year":"2009","unstructured":"Osterholzer, J. J. et al. Accumulation of CD11b\u2009+\u2009lung dendritic cells in response to fungal infection results from the CCR2-mediated recruitment and differentiation of Ly-6Chigh monocytes. Journal of immunology (Baltimore, Md. 1950) \n                           183, 8044\u20138053, doi:10.4049\/jimmunol.0902823 (2009).","journal-title":"Journal of immunology (Baltimore, Md. 1950)"},{"key":"11271_CR39","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/7403","volume":"5","author":"NC Fernandez","year":"1999","unstructured":"Fernandez, N. C. et al. Dendritic cells directly trigger NK cell functions: Cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med \n                           5, 405\u2013411 (1999).","journal-title":"Nat Med"},{"key":"11271_CR40","first-page":"17","volume":"311","author":"RM Steinman","year":"2006","unstructured":"Steinman, R. M. & Hemmi, H. Dendritic cells: translating innate to adaptive immunity. Current topics in microbiology and immunology \n                           311, 17\u201358 (2006).","journal-title":"Current topics in microbiology and immunology"},{"key":"11271_CR41","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/nri1845","volume":"6","author":"C Reis e Sousa","year":"2006","unstructured":"Reis e Sousa, C. Dendritic cells in a mature age. Nat Rev Immunol \n                           6, 476\u2013483 (2006).","journal-title":"Nat Rev Immunol"},{"key":"11271_CR42","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1084\/jem.185.2.317","volume":"185","author":"C Winzler","year":"1997","unstructured":"Winzler, C. et al. Maturation Stages of Mouse Dendritic Cells in Growth Factor\u2013dependent Long-Term Cultures. The Journal of Experimental Medicine \n                           185, 317\u2013328, doi:10.1084\/jem.185.2.317 (1997).","journal-title":"The Journal of Experimental Medicine"},{"key":"11271_CR43","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1128\/IAI.66.3.1121-1126.1998","volume":"66","author":"Y Lin","year":"1998","unstructured":"Lin, Y., Zhang, M. & Barnes, P. F. Chemokine Production by a Human Alveolar Epithelial Cell Line in Response to Mycobacterium tuberculosis. Infection and Immunity \n                           66, 1121\u20131126 (1998).","journal-title":"Infection and Immunity"},{"key":"11271_CR44","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/nature01322","volume":"420","author":"LM Coussens","year":"2002","unstructured":"Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature \n                           420, 860\u2013867 (2002).","journal-title":"Nature"},{"key":"11271_CR45","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.coi.2010.01.021","volume":"22","author":"E Peranzoni","year":"2010","unstructured":"Peranzoni, E. et al. Myeloid-derived suppressor cell heterogeneity and subset definition. Current Opinion in Immunology \n                           22, 238\u2013244, doi:10.1016\/j.coi.2010.01.021 (2010).","journal-title":"Current Opinion in Immunology"},{"key":"11271_CR46","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s002620050603","volume":"49","author":"DA Arenberg","year":"2000","unstructured":"Arenberg, D. A. et al. Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines. Cancer Immunol Immunother \n                           49, 63\u201370 (2000).","journal-title":"Cancer Immunol Immunother"},{"key":"11271_CR47","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/bit.22671","volume":"106","author":"D Mazzei","year":"2010","unstructured":"Mazzei, D., Guzzardi, M. A., Giusti, S. & Ahluwalia, A. A low shear stress modular bioreactor for connected cell culture under high flow rates. Biotechnology and bioengineering \n                           106, 127\u2013137, doi:10.1002\/bit.22671 (2010).","journal-title":"Biotechnology and bioengineering"},{"key":"11271_CR48","doi-asserted-by":"publisher","first-page":"7497","DOI":"10.4049\/jimmunol.173.12.7497","volume":"173","author":"D Wilflingseder","year":"2004","unstructured":"Wilflingseder, D. et al. HIV-1-Induced Migration of Monocyte-Derived Dendritic Cells Is Associated with Differential Activation of MAPK Pathways. The Journal of Immunology \n                           173, 7497\u20137505, doi:10.4049\/jimmunol.173.12.7497 (2004).","journal-title":"The Journal of Immunology"},{"key":"11271_CR49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000976","volume":"6","author":"SM Leal Jr.","year":"2010","unstructured":"Leal, S. M. Jr. et al. Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis. PLoS Pathog \n                           6, e1000976, doi:10.1371\/journal.ppat.1000976 (2010).","journal-title":"PLoS Pathog"},{"key":"11271_CR50","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1128\/EC.00178-06","volume":"5","author":"G Reyes","year":"2006","unstructured":"Reyes, G., Romans, A., Nguyen, C. K. & May, G. S. Novel mitogen-activated protein kinase MpkC of Aspergillus fumigatus is required for utilization of polyalcohol sugars. Eukaryot Cell \n                           5, 1934\u20131940, doi:10.1128\/EC.00178-06 (2006).","journal-title":"Eukaryot Cell"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11271-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11271-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11271-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T10:57:38Z","timestamp":1671793058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11271-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,14]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["11271"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-11271-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,14]]},"assertion":[{"value":"22 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"11644"}}