Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages

Lim, Jenson; Coates, Christopher; 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.

doi:10.4049/jimmunol.1700790

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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
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URI:	https://cronfa.swan.ac.uk/Record/cronfa39003
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first_indexed	2018-03-08T22:02:09Z
last_indexed	2020-06-18T18:53:37Z
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spelling	2020-06-18T15:19:36.5332502 v2 39003 2018-03-08 Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages af160934b75bea5b8ba83d68b3d1a003 Christopher Coates Christopher Coates true false 2018-03-08 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. Journal Article The Journal of Immunology 200 10 3539 3546 0022-1767 1550-6606 15 5 2018 2018-05-15 10.4049/jimmunol.1700790 http://www.jimmunol.org/content/early/2018/04/10/jimmunol.1700790 COLLEGE NANME COLLEGE CODE Swansea University 2020-06-18T15:19:36.5332502 2018-03-08T20:11:44.6340385 Faculty of Science and Engineering School of Biosciences, Geography and Physics - Biosciences Jenson Lim 1 Christopher Coates 2 Paula I. Seoane 3 Mariam Garelnabi 4 Leanne M. Taylor-Smith 5 Pauline Monteith 6 Camille L. Macleod 7 Claire J. Escaron 8 Gordon D. Brown 9 Rebecca A. Hall 10 Robin C. May 11 0039003-03052018093401.pdf 39003.pdf 2018-05-03T09:34:01.8030000 Output 1836790 application/pdf Version of Record true 2018-05-03T00:00:00.0000000 Released under the terms of a Creative Commons Attribution 4.0 License (CC-BY). true eng
title	Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages
spellingShingle	Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages Christopher Coates
title_short	Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages
title_full	Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages
title_fullStr	Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages
title_full_unstemmed	Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages
title_sort	Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages
author_id_str_mv	af160934b75bea5b8ba83d68b3d1a003
author_id_fullname_str_mv	af160934b75bea5b8ba83d68b3d1a003_***_Christopher Coates
author	Christopher Coates
author2	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
format	Journal article
container_title	The Journal of Immunology
container_volume	200
container_issue	10
container_start_page	3539
publishDate	2018
institution	Swansea University
issn	0022-1767 1550-6606
doi_str_mv	10.4049/jimmunol.1700790
college_str	Faculty of Science and Engineering
hierarchytype
hierarchy_top_id	facultyofscienceandengineering
hierarchy_top_title	Faculty of Science and Engineering
hierarchy_parent_id	facultyofscienceandengineering
hierarchy_parent_title	Faculty of Science and Engineering
department_str	School of Biosciences, Geography and Physics - Biosciences{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Biosciences, Geography and Physics - Biosciences
url	http://www.jimmunol.org/content/early/2018/04/10/jimmunol.1700790
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description	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.
published_date	2018-05-15T03:49:29Z
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score	11.016235

Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages

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