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Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages

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., and others. (2018) Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages. The Journal of Immunology, 200 (10). pp. 3539-3546. ISSN 0022-1767. (doi:10.4049/jimmunol.1700790) (KAR id:91840)

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Official URL:
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.

Item Type: Article
DOI/Identification number: 10.4049/jimmunol.1700790
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Becky Hall
Date Deposited: 01 Dec 2021 09:01 UTC
Last Modified: 02 Dec 2021 22:45 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91840 (The current URI for this page, for reference purposes)
Hall, Rebecca A.: https://orcid.org/0000-0002-4908-8168
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