Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion
Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion
复制标题
DOI：
10.1038/s41467-019-13298-9
复制
发表时间：
2019-11-22
影响因子：
16.6
通讯作者：
Brown, Alistair J. P.
中科院分区：
文献类型：
--
作者：
Pradhan, Arnab;Avelar, Gabriela M.;Brown, Alistair J. P.
为了在宿主中定居，病原体必须应对当地的环境和免疫挑战。在这里，我们揭示了真菌病原体白色念珠菌利用不同的宿主相关信号，通过掩盖主要病原体相关分子模式（PAMP）β-葡聚糖来促进免疫逃避。某些营养物质、压力和抗真菌药物会触发β-葡聚糖掩蔽，而其他输入，如氮源和群体感应分子，对这种PAMP的影响有限。特别是，铁限制引发细胞壁的实质性变化，从而减少β-葡聚糖暴露。这与巨噬细胞的吞噬作用降低和外周血单核细胞的细胞因子应答减弱有关。铁限制诱导的β-葡聚糖掩蔽依赖于通过铁受体Ftr 1和铁响应转录因子Sef 1以及蛋白激酶A途径的平行信号传导。我们的数据显示C.白色念珠菌利用多种多样的特异性宿主信号来触发针对即将发生的吞噬攻击的保护性预期反应并促进宿主定殖。
To colonise their host, pathogens must counter local environmental and immunological challenges. Here, we reveal that the fungal pathogen Candida albicans exploits diverse host-associated signals to promote immune evasion by masking of a major pathogen-associated molecular pattern (PAMP), beta-glucan. Certain nutrients, stresses and antifungal drugs trigger beta-glucan masking, whereas other inputs, such as nitrogen sources and quorum sensing molecules, exert limited effects on this PAMP. In particular, iron limitation triggers substantial changes in the cell wall that reduce beta-glucan exposure. This correlates with reduced phagocytosis by macrophages and attenuated cytokine responses by peripheral blood mononuclear cells. Iron limitation-induced beta-glucan masking depends on parallel signalling via the iron transceptor Ftr1 and the iron-responsive transcription factor Sef1, and the protein kinase A pathway. Our data reveal that C. albicans exploits a diverse range of specific host signals to trigger protective anticipatory responses against impending phagocytic attack and promote host colonisation.