{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:44:17Z","timestamp":1792665857897,"version":"4.5.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":2501,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The pathogenic fungus Cryptococcus enters the human host via inhalation into the lung and is able to reside in a niche environment that is serum- (opsonin) limiting. Little is known about the mechanism by which nonopsonic phagocytosis occurs via phagocytes in such situations. Using a combination of soluble inhibitors of phagocytic receptors and macrophages derived from knockout mice and human volunteers, we show that uptake of nonopsonized Cryptococcus neoformans and C. gattii via the mannose receptor is dependent on macrophage activation by cytokines. However, although uptake of C. neoformans is via both dectin-1 and dectin-2, C. gattii uptake occurs largely via dectin-1. Interestingly, dectin inhibitors also blocked phagocytosis of unopsonized Cryptococci in wax moth (Galleria mellonella) larvae and partially protected the larvae from infection by both fungi, supporting a key role for host phagocytes in augmenting early disease establishment. Finally, we demonstrated that internalization of nonopsonized Cryptococci is not accompanied by the nuclear translocation of NF-\u03baB or its concomitant production of proinflammatory cytokines such as TNF-\u03b1. Thus, nonopsonized Cryptococci are recognized by mammalian phagocytes in a manner that minimizes proinflammatory cytokine production and potentially facilitates fungal pathogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.1700790","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T16:57:16Z","timestamp":1523465836000},"page":"3539-3546","source":"Crossref","is-referenced-by-count":36,"title":["Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-356X","authenticated-orcid":false,"given":"Jenson","family":"Lim","sequence":"first","affiliation":[{"name":"Biological and Environmental Sciences, University of Stirling , Stirling FK9 4LA,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-4369","authenticated-orcid":false,"given":"Christopher J","family":"Coates","sequence":"additional","affiliation":[{"name":"Department of Biosciences, College of Science, Swansea University , Swansea SA2 8PP, Wales,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6323-5470","authenticated-orcid":false,"given":"Paula I","family":"Seoane","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, School of Biosciences, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9948-8242","authenticated-orcid":false,"given":"Mariam","family":"Garelnabi","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, School of Biosciences, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6217-6499","authenticated-orcid":false,"given":"Leanne M","family":"Taylor-Smith","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, School of Biosciences, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1447-9484","authenticated-orcid":false,"given":"Pauline","family":"Monteith","sequence":"additional","affiliation":[{"name":"Biological and Environmental Sciences, University of Stirling , Stirling FK9 4LA,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille L","family":"Macleod","sequence":"additional","affiliation":[{"name":"Biological and Environmental Sciences, University of Stirling , Stirling FK9 4LA,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6588-6805","authenticated-orcid":false,"given":"Claire J","family":"Escaron","sequence":"additional","affiliation":[{"name":"Protein Reference Unit, South West London Pathology, St. George\u2019s University Hospitals NHS Foundation Trust , London SW17 0QT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon D","family":"Brown","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen , Aberdeen AB25 2ZD,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-8168","authenticated-orcid":false,"given":"Rebecca A","family":"Hall","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, School of Biosciences, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5364-1838","authenticated-orcid":false,"given":"Robin C","family":"May","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, School of Biosciences, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"2025030610150574100_r1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nrmicro1245","article-title":"Deciphering the model pathogenic fungus Cryptococcus neoformans","volume":"3","author":"Idnurm","year":"2005","journal-title":"Nat. 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