{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:07:22Z","timestamp":1788300442612,"version":"build-2803163510"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen but the cell signaling pathways that drive T cell responses regulating antifungal immunity are incompletely understood. Notch is a key signaling pathway regulating T cell development, and differentiation and functional responses of mature T cells in the periphery. The targeting of Notch signaling within T cells has been proposed as a potential treatment for alloimmune and autoimmune disorders, but it is unknown whether disturbances to T cell immunity may render these patients vulnerable to fungal infections. To elucidate the role of Notch signaling during fungal infections, we infected mice expressing the pan-Notch inhibitor dominant negative mastermind-like within mature T cells with C. neoformans. Inhibition of T cell\u2013restricted Notch signaling increased fungal burdens in the lungs and CNS, diminished pulmonary leukocyte recruitment, and simultaneously impaired Th1 and Th2 responses. Pulmonary leukocyte cultures from T cell Notch-deprived mice produced less IFN-\u03b3, IL-5, and IL-13 than wild-type cells. This correlated with lower frequencies of IFN-\u03b3\u2013, IL-5\u2013, and IL-13\u2013producing CD4+ T cells, reduced expression of Th1 and Th2 associated transcription factors, Tbet and GATA3, and reduced production of IFN-\u03b3 by CD8+ T cells. In contrast, Th17 responses were largely unaffected by Notch signaling. The changes in T cell responses corresponded with impaired macrophage activation and reduced leukocyte accumulation, leading to diminished fungal control. These results identify Notch signaling as a previously unappreciated regulator of Th1 and Th2 immunity and an important element of antifungal defenses against cryptococcal infection and CNS dissemination.<\/jats:p>","DOI":"10.4049\/jimmunol.1601715","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T20:40:24Z","timestamp":1497472824000},"page":"643-655","source":"Crossref","is-referenced-by-count":28,"title":["T Cell\u2013Restricted Notch Signaling Contributes to Pulmonary Th1 and Th2 Immunity during\n                    <i>Cryptococcus neoformans<\/i>\n                    Infection"],"prefix":"10.1093","volume":"199","author":[{"given":"Lori M","family":"Neal","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48109"},{"name":"Research Service, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4211-0817","authenticated-orcid":false,"given":"Yafeng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jooho","family":"Chung","sequence":"additional","affiliation":[{"name":"Graduate Program in Cell and Molecular Biology, University of Michigan , Ann Arbor, MI 48109"},{"name":"Medical Scientist Training Program, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enze","family":"Xing","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woosung","family":"Cho","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni N","family":"Malachowski","sequence":"additional","affiliation":[{"name":"Research Service, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley R","family":"Sandy-Sloat","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Osterholzer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48109"},{"name":"Research Service, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1312-6748","authenticated-orcid":false,"given":"Ivan","family":"Maillard","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan , Ann Arbor, MI 48109"},{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"},{"name":"Department of Cell and Developmental Biology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-0843","authenticated-orcid":false,"given":"Michal A","family":"Olszewski","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48109"},{"name":"Research Service, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,15]]},"reference":[{"key":"2025030614185134100_r1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/QAD.0b013e328322ffac","article-title":"Estimation of the current global burden of cryptococcal meningitis among persons living with HIV\/AIDS","volume":"23","author":"Park","year":"2009","journal-title":"AIDS"},{"key":"2025030614185134100_r2","first-page":"61","article-title":"Cryptococcal infections in non-HIV-infected patients","volume":"124","author":"Pappas","year":"2013","journal-title":"Trans. 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Immunol."},{"key":"2025030614185134100_r6","doi-asserted-by":"crossref","first-page":"774","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. 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J. Pathol."},{"key":"2025030614185134100_r10","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. 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Immunol."},{"key":"2025030614185134100_r35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.immuni.2007.05.021","article-title":"Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch","volume":"27","author":"Amsen","year":"2007","journal-title":"Immunity"},{"key":"2025030614185134100_r36","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.immuni.2007.04.018","article-title":"Notch directly regulates Gata3 expression during T helper 2 cell differentiation","volume":"27","author":"Fang","year":"2007","journal-title":"Immunity"},{"key":"2025030614185134100_r37","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.4049\/jimmunol.1402837","article-title":"The Notch signaling pathway controls short-lived effector CD8+ T cell differentiation but is dispensable for memory generation","volume":"194","author":"Mathieu","year":"2015","journal-title":"J. Immunol."},{"key":"2025030614185134100_r38","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1182\/blood-2010-03-271940","article-title":"Notch signaling is a critical regulator of allogeneic CD4+ T-cell responses mediating graft-versus-host disease","volume":"117","author":"Zhang","year":"2011","journal-title":"Blood"},{"key":"2025030614185134100_r39","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1172\/JCI65477","article-title":"Blockade of individual Notch ligands and receptors controls graft-versus-host disease","volume":"123","author":"Tran","year":"2013","journal-title":"J. Clin. Invest."},{"key":"2025030614185134100_r40","doi-asserted-by":"crossref","first-page":"5990","DOI":"10.4049\/jimmunol.179.9.5990","article-title":"JAGGED1 and delta1 differentially regulate the outcome of experimental autoimmune encephalomyelitis","volume":"179","author":"Elyaman","year":"2007","journal-title":"J. Immunol."},{"key":"2025030614185134100_r41","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.ajpath.2013.12.010","article-title":"Blockade of Notch signaling ameliorates murine collagen-induced arthritis via suppressing Th1 and Th17 cell responses","volume":"184","author":"Jiao","year":"2014","journal-title":"Am. J. Pathol."},{"key":"2025030614185134100_r42","doi-asserted-by":"crossref","first-page":"996","DOI":"10.4049\/jimmunol.1301991","article-title":"STAT5-induced lunatic fringe during Th2 development alters delta-like 4-mediated Th2 cytokine production in respiratory syncytial virus-exacerbated airway allergic disease","volume":"192","author":"Mukherjee","year":"2014","journal-title":"J. Immunol."},{"key":"2025030614185134100_r43","doi-asserted-by":"crossref","first-page":"258168","DOI":"10.1155\/2015\/258168","article-title":"\u03b3-secretase inhibitor alleviates acute airway inflammation of allergic asthma in mice by downregulating Th17 cell differentiation","volume":"2015","author":"Zhang","year":"2015","journal-title":"Mediators Inflamm."},{"key":"2025030614185134100_r44","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.4049\/jimmunol.1402034","article-title":"Transient blockade of delta-like Notch ligands prevents allograft rejection mediated by cellular and humoral mechanisms in a mouse model of heart transplantation","volume":"194","author":"Wood","year":"2015","journal-title":"J. Immunol."},{"key":"2025030614185134100_r45","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.4049\/jimmunol.1004076","article-title":"Blockade of Notch ligand \u03b41 promotes allograft survival by inhibiting alloreactive Th1 cells and cytotoxic T cell generation","volume":"187","author":"Riella","year":"2011","journal-title":"J. Immunol."},{"key":"2025030614185134100_r46","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/eji.201243151","article-title":"Jagged2-signaling promotes IL-6-dependent transplant rejection","volume":"43","author":"Riella","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"2025030614185134100_r47","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.4049\/jimmunol.1100725","article-title":"Notch ligand delta-like 4 blockade alleviates experimental autoimmune encephalomyelitis by promoting regulatory T cell development","volume":"187","author":"Bassil","year":"2011","journal-title":"J. Immunol."},{"key":"2025030614185134100_r48","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jneuroim.2012.08.003","article-title":"Therapeutic effects of anti-Delta1 mAb on Theiler\u2019s murine encephalomyelitis virus-induced demyelinating disease","volume":"252","author":"Tsugane","year":"2012","journal-title":"J. Neuroimmunol."},{"key":"2025030614185134100_r49","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1164\/rccm.200806-893OC","article-title":"Gamma-secretase inhibitor reduces allergic pulmonary inflammation by modulating Th1 and Th2 responses","volume":"179","author":"Kang","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025030614185134100_r50","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1084\/jem.20050923","article-title":"Notch signaling is an important regulator of type 2 immunity","volume":"202","author":"Tu","year":"2005","journal-title":"J. Exp. 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Med."},{"key":"2025030614185134100_r52","doi-asserted-by":"crossref","first-page":"e1002341","DOI":"10.1371\/journal.ppat.1002341","article-title":"The critical role of Notch ligand Delta-like 1 in the pathogenesis of influenza A virus (H1N1) infection","volume":"7","author":"Ito","year":"2011","journal-title":"PLoS Pathog."},{"key":"2025030614185134100_r53","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1074-7613(03)00270-X","article-title":"Delta1-Notch3 interactions bias the functional differentiation of activated CD4+ T cells","volume":"19","author":"Maekawa","year":"2003","journal-title":"Immunity"},{"key":"2025030614185134100_r54","doi-asserted-by":"crossref","first-page":"e00436-16","DOI":"10.1128\/mBio.00436-16","article-title":"Transcription factor KLF2 in dendritic cells downregulates Th2 programming via the HIF-1\u03b1\/Jagged2\/Notch axis","volume":"7","author":"Xiong","year":"2016","journal-title":"MBio"},{"key":"2025030614185134100_r55","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1084\/jem.20062648","article-title":"Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen","volume":"204","author":"Caton","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025030614185134100_r56","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.immuni.2011.08.013","article-title":"Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine","volume":"35","author":"Lewis","year":"2011","journal-title":"Immunity"},{"key":"2025030614185134100_r57","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1084\/jem.173.4.793","article-title":"Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells","volume":"173","author":"Huffnagle","year":"1991","journal-title":"J. Exp. Med."},{"key":"2025030614185134100_r58","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/jlb.55.1.35","article-title":"The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection","volume":"55","author":"Huffnagle","year":"1994","journal-title":"J. Leukoc. 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