{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:40:24Z","timestamp":1789922424913,"version":"4.0.1"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Neutrophils have been shown to efficiently kill<jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>, a causative agent of meningoencephalitis. Here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>and the underlying mechanisms in real time. Neutrophils were directly seen to chase<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>cells and then rapidly internalize them. Complement C5a-C5aR signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of the organisms. The addition of recombinant complement C5a enhanced neutrophil movement but did not induce chemotaxis, suggesting that the C5a gradient is crucial. Incubation with<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>resulted in enhanced activation of Erk and p38 mitogen-activated protein (MAP) kinases (MAPKs) in neutrophils. Inhibition of the p38 MAPK pathway, but not the Erk pathway, significantly impaired neutrophil migration and its subsequent killing of<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>. Deficiency of CD11b or blocking of CD11b did not affect the migration of neutrophils toward<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>but almost completely abolished phagocytosis and killing of the organisms by neutrophils. C5a-C5aR signaling induced enhanced surface expression of CD11b. Interestingly, the original surface expression of CD11b was essential and sufficient for neutrophils to attach to<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>but was unable to mediate phagocytosis. In contrast, the enhanced surface expression of CD11b induced by C5a-C5aR signaling was essential for neutrophil phagocytosis and subsequent killing of yeast cells. Collectively, this is the first report of the dynamic interactions of neutrophils with<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>, demonstrating a crucial role of C5a-C5aR signaling in neutrophil killing of<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>in real time.<\/jats:p>","DOI":"10.1128\/iai.01197-15","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T02:14:06Z","timestamp":1445912046000},"page":"216-229","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Real-Time Imaging of Interactions of Neutrophils with Cryptococcus neoformans Demonstrates a Crucial Role of Complement C5a-C5aR Signaling"],"prefix":"10.1128","volume":"84","author":[{"given":"Donglei","family":"Sun","sequence":"first","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingshun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"},{"name":"Department of Immunology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gongguan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/125.4.367"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.43.2.574-579.1984"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00039-10"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-015-1192-3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.1.24-28.1991"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015587"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00193"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep08008"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.4049\/jimmunol.156.10.3836","article-title":"Oxidative killing of Cryptococcus neoformans by human neutrophils. 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