Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor
Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor
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DOI：
10.1073/pnas.0609848104
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发表时间：
2007-01-23
影响因子：
11.1
通讯作者：
Goldman, William E.
中科院分区：
文献类型：
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作者：
Rappleye, Chad A.;Groppe Eissenberg, Linda;Goldman, William E.
真菌病原体的成功感染取决于宿主免疫机制的破坏，该机制检测保守的细胞壁成分，如β-葡聚糖。一种不太常见的多糖，α-（1，3）-葡聚糖，是大多数真菌呼吸道病原体的细胞壁成分，并与致病性相关或直接与毒力相关。然而，α-（1，3）-葡聚糖促进真菌毒力的确切机制尚不清楚。在这里，我们表明，α-（1，3）-葡聚糖存在于荚膜组织胞浆菌酵母细胞壁的最外层，并通过隐藏宿主吞噬细胞检测到的免疫刺激性β-葡聚糖而导致发病。通过酵母细胞上存在α-（1，3）-葡聚糖层或通过基于RNA干扰的宿主β-葡聚糖受体dectin-1的消耗，抑制吞噬细胞产生促炎性TNF α。因此，我们在功能上确定了影响组织胞浆菌病中宿主-病原体相互作用的关键分子组分，并揭示了H。荚膜阻碍宿主免疫系统。此外，我们建议，这种逃避的程度有助于二型真菌病原体和机会真菌之间的致病潜力的差异。
Successful infection by fungal pathogens depends on subversion of host immune mechanisms that detect conserved cell wall components such as beta-glucans. A less common polysaccharide, alpha-(1,3)-glucan, is a cell wall constituent of most fungal respiratory pathogens and has been correlated with pathogenicity or linked directly to virulence. However, the precise mechanism by which alpha-(1,3)-glucan promotes fungal virulence is unknown. Here, we show that alpha-(1,3)-glucan is present in the outermost layer of the Histoplasma capsulatum yeast cell wall and contributes to pathogenesis by concealing immunostimulatory beta-glucans from detection by host phagocytic cells. Production of proinflammatory TNF alpha by phagocytes was suppressed either by the presence of the alpha-(1,3)-glucan layer on yeast cells or by RNA interference based depletion of the host beta-glucan receptor dectin-1. Thus, we have functionally defined key molecular components influencing the initial host-pathogen interaction in histoplasmosis and have revealed an important mechanism by which H. capsulatum thwarts the host immune system. Furthermore, we propose that the degree of this evasion contributes to the difference in pathogenic potential between dimorphic fungal pathogens and opportunistic fungi.