Department of Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Geert Grootplein 8, 6525 GA, Nijmegen, The Netherlands.
Immunobiology. 2010 Nov;215(11):915-20. doi: 10.1016/j.imbio.2009.10.002. Epub 2009 Nov 25.
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 β-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.
黑色素生物色素与真菌毒力有关。烟曲霉分生孢子被黑色素化，免疫原性较弱。我们表明，静止烟曲霉分生孢子表面的黑色素颜料可能用于掩盖病原体相关分子模式 (PAMP) 诱导的细胞因子反应。与黑色素化的野生型分生孢子相比，白化分生孢子在人外周血单核细胞 (PBMC) 中诱导产生了更多的促炎细胞因子。阻断 dectin-1 受体、Toll 样受体 4 或甘露糖受体可减少白化分生孢子诱导的细胞因子产生，但不能减少野生型分生孢子诱导的细胞因子产生。此外，与从健康供体分离的细胞的刺激相比，白化分生孢子在分离自 dectin-1 缺陷个体的 PBMC 中刺激细胞因子产生的能力较弱。这些结果表明，β-葡聚糖，以及其他刺激 PAMP，如甘露聚糖衍生物，在没有黑色素的情况下暴露在分生孢子表面。黑色素可能通过阻碍宿主免疫细胞对烟曲霉上特定配体的反应能力来发挥调节作用。
