Aspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response

被引:99
作者
Chai, Louis Y. A. [1 ,2 ,3 ]
Netea, Mihai G. [1 ,2 ]
Sugui, Janyce [4 ]
Vonk, Alieke G. [5 ]
van de Sande, Wendy W. J. [5 ]
Warris, Adilia [2 ,6 ]
Kwon-Chung, Kyung J. [4 ]
Kullberg, Bart Jan [1 ,2 ]
机构
[1] Radboud Univ Nijmegen Med Ctr, Dept Med, NL-6525 GA Nijmegen, Netherlands
[2] Nijmegen Inst Infect Inflammat & Immun N4i, Nijmegen, Netherlands
[3] Natl Univ Singapore Hosp, Dept Med, Singapore 119074, Singapore
[4] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA
[5] Erasmus MC, Univ Med Ctr Rotterdam, Dept Med Microbiol & Infect Dis, NL-3015 CE Rotterdam, Netherlands
[6] Radboud Univ Nijmegen Med Ctr, Dept Pediat, Nijmegen, Netherlands
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
beta-glucan; Dectin-1; Mannose receptor; Mannan; Melanin; Modulation; CANDIDA-ALBICANS; PIGMENT BIOSYNTHESIS; IMMUNE RECOGNITION; BETA-GLUCAN; VIRULENCE; GENE; DECTIN-1; MACROPHAGES; RECEPTOR;
D O I
10.1016/j.imbio.2009.10.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Melanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine response. The albino conidia induced significantly more proinflammatory cytokines in human peripheral blood mononuclear cells (PBMC), as compared to melanised wild-type conidia. Blocking dectin-1 receptor, Toll-like receptor 4 or mannose receptor decreased cytokine production induced by the albino but not by the wild type conidia. Moreover, albino conidia stimulated less potently, cytokine production in PBMC isolated from an individual with defective dectin-1, compared to the stimulation of cells isolated from healthy donors. These results suggest that beta-glucans, but also other stimulatory PAMPs like mannan derivatives, are exposed on conidial surface in the absence of melanin. Melanin may play a modulatory role by impeding the capability of host immune cells to respond to specific ligands on A. fumigatus. (C) 2009 Elsevier GmbH. All rights reserved.
引用
收藏
页码:915 / 920
页数:6
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