Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/27122
Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages
Author(s): Lim, Jenson
Coates, Christopher J
Seoane, Paula I
Garelnabi, Mariam
Taylor-Smith, Leanne M
Monteith, Pauline
Macleod, Camille L
Escaron, Claire J
Brown, Gordon D
Hall, Rebecca A
May, Robin C
Issue Date: 15-May-2018
Citation: Lim J, Coates CJ, Seoane PI, Garelnabi M, Taylor-Smith LM, Monteith P, Macleod CL, Escaron CJ, Brown GD, Hall RA & May RC (2018) Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages. Journal of Immunology, 200 (10), pp. 3539-3546. https://doi.org/10.4049/jimmunol.1700790.
Abstract: 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-κB or its concomitant production of proinflammatory cytokines such as TNF-α. Thus, nonopsonized Cryptococci are recognized by mammalian phagocytes in a manner that minimizes proinflammatory cytokine production and potentially facilitates fungal pathogenesis.
DOI Link: 10.4049/jimmunol.1700790
Rights: his article is distributed under the terms of the CC BY 4.0 Unported license (https://creativecommons.org/licenses/by/4.0/)

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