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Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages

Jenson Lim, Christopher Coates, Paula I. Seoane, Mariam Garelnabi, Leanne M. Taylor-Smith, Pauline Monteith, Camille L. Macleod, Claire J. Escaron, Gordon D. Brown, Rebecca A. Hall, Robin C. May

The Journal of Immunology, Volume: 200, Issue: 10, Pages: 3539 - 3546

Swansea University Author: Christopher Coates

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DOI (Published version): 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 non-opsonic phagocytosis occurs via phagocytes in such situations. Using a combination of...

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Published in: The Journal of Immunology
ISSN: 0022-1767 1550-6606
Published: 2018
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa39003
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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 non-opsonic phagocytosis occurs via phagocytes in such situations. Using a combination of soluble inhibitors of phagocytic receptors and macrophages derived from knockout mice, we show that uptake of non-opsonised Cryptococcus neoformans and Cryptocccous gattii is not mannose receptor dependent. However, while uptake of C. neoformans is via both dectin-1 and dectin-2, C. gattii uptake occurs largely via dectin-1. This is further confirmed using insect immune cells (haemocytes) from the wax moth (Galleria mellonella) larvae model with soluble inhibitors. Interestingly, dectin inhibitors blocked phagocytosis of unopsonised Cryptococci 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 internalisation of non-opsonised Cryptococci is not accompanied by the nuclear translocation of NFB or its concomitant production of proinflammatory cytokines such as TNF. Thus, non-opsonised Cryptococci are recognised by mammalian phagocytes in a manner that minimises proinflammatory cytokine production and potentially facilitates fungal pathogenesis.
College: Faculty of Science and Engineering
Issue: 10
Start Page: 3539
End Page: 3546

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