Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages

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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.; May, Robin C.

In: Journal of Immunology, Vol. 200, No. 9, 15.05.2018, p. 3539-3546.

Research output: Contribution to journalArticlepeer-review

Harvard

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, vol. 200, no. 9, pp. 3539-3546. https://doi.org/10.4049/jimmunol.1700790

APA

Lim, J., Coates, C. J., Seoane, P. I., Garelnabi, M., Taylor-Smith, L. M., Monteith, P., Macleod, C. L., Escaron, C. J., Brown, G. D., Hall, R. A., & May, R. C. (2018). Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages. Journal of Immunology, 200(9), 3539-3546. https://doi.org/10.4049/jimmunol.1700790

Vancouver

Author

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. / Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages. In: Journal of Immunology. 2018 ; Vol. 200, No. 9. pp. 3539-3546.

Bibtex

@article{dff11fa3472b434f902c5703ff9fd31e,
title = "Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages",
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.",
keywords = "Journal Article",
author = "Jenson Lim and Coates, {Christopher J.} and Seoane, {Paula I.} and Mariam Garelnabi and Taylor-Smith, {Leanne M} and Pauline Monteith and Macleod, {Camille L} and Escaron, {Claire J} and Brown, {Gordon D} and Hall, {Rebecca A.} and May, {Robin C}",
note = "Copyright {\textcopyright} 2018 The Authors.",
year = "2018",
month = may,
day = "15",
doi = "10.4049/jimmunol.1700790",
language = "English",
volume = "200",
pages = "3539--3546",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

RIS

TY - JOUR

T1 - Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages

AU - Lim, Jenson

AU - Coates, Christopher J.

AU - Seoane, Paula I.

AU - Garelnabi, Mariam

AU - Taylor-Smith, Leanne M

AU - Monteith, Pauline

AU - Macleod, Camille L

AU - Escaron, Claire J

AU - Brown, Gordon D

AU - Hall, Rebecca A.

AU - May, Robin C

N1 - Copyright © 2018 The Authors.

PY - 2018/5/15

Y1 - 2018/5/15

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.4049/jimmunol.1700790

DO - 10.4049/jimmunol.1700790

M3 - Article

C2 - 29643192

VL - 200

SP - 3539

EP - 3546

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -