Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida.
Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida.
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DOI：
10.1038/s41467-018-03014-4
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发表时间：
2018-02-21
影响因子：
16.6
通讯作者：
Mody CH
中科院分区：
文献类型：
--
作者：
Li SS;Ogbomo H;Mansour MK;Xiang RF;Szabo L;Munro F;Mukherjee P;Mariuzza RA;Amrein M;Vyas JM;Robbins SM;Mody CH
自然杀伤细胞（NK）利用激活受体NKp30作为微生物模式识别受体，识别、激活细胞溶解途径，直接杀死真菌新型隐球菌和白色念珠菌。然而，触发nkp30介导的杀伤的真菌病原体相关分子模式（PAMP）仍有待确定。我们发现真菌细胞壁的成分β-1,3-葡聚糖与NKp30结合。我们进一步证明β-1,3-葡聚糖刺激颗粒的收敛和极化，正如活细胞成像所显示的那样。通过Src家族激酶信号传导，β-1,3-葡聚糖增加NKp30在微生物和NK细胞突触的表达和聚集，诱导穿孔素释放，产生真菌细胞毒性。可溶性β-1,3-葡聚糖并没有阻断真菌和NK细胞之间的相互作用，而是增强了真菌的杀伤能力，并恢复了hiv阳性个体NK细胞对有缺陷的隐球菌的杀伤能力，这表明β-1,3-葡聚糖既是一种激活配体，也是一种可溶的PAMP，可以塑造NK细胞的宿主免疫力。自然杀伤（NK）细胞已被证明通过激活受体NKp30介导真菌的杀伤，但NKp30的真菌靶点尚不清楚。在这里，作者通过原子力显微镜和活细胞成像显示，β-1,3-葡聚糖由新型隐球菌和白色念珠菌表达，并负责nkp30介导的NK杀伤。
Natural killer (NK) cells use the activating receptor NKp30 as a microbial pattern-recognition receptor to recognize, activate cytolytic pathways, and directly kill the fungi Cryptococcus neoformans and Candida albicans. However, the fungal pathogen-associated molecular pattern (PAMP) that triggers NKp30-mediated killing remains to be identified. Here we show that β-1,3-glucan, a component of the fungal cell wall, binds to NKp30. We further demonstrate that β-1,3-glucan stimulates granule convergence and polarization, as shown by live cell imaging. Through Src Family Kinase signaling, β-1,3-glucan increases expression and clustering of NKp30 at the microbial and NK cell synapse to induce perforin release for fungal cytotoxicity. Rather than blocking the interaction between fungi and NK cells, soluble β-1,3-glucan enhances fungal killing and restores defective cryptococcal killing by NK cells from HIV-positive individuals, implicating β-1,3-glucan to be both an activating ligand and a soluble PAMP that shapes NK cell host immunity. Natural killer (NK) cells has been show to mediate fungi killing via the activating receptor NKp30, but the fungal target for NKp30 is still unclear. Here the authors show, using atomic force microscopy and live cell imaging, that β-1,3-glucan is expressed by Cryptococcus neoformans and Candida albicans and responsible for NKp30-mediated NK killing.
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影响因子：
6.7
作者：
Islam A;Li SS;Oykhman P;Timm-McCann M;Huston SM;Stack D;Xiang RF;Kelly MM;Mody CH
通讯作者：
Mody CH
影响因子：
--
作者：
Dellinger, EP;Babineau, TJ;Condon, RE
通讯作者：
Condon, RE
影响因子：
6.4
作者：
HORN, CA;WASHBURN, RG
通讯作者：
WASHBURN, RG
影响因子：
9
作者：
BABINEAU, TJ;MARCELLO, P;FORSE, RA
通讯作者：
FORSE, RA
影响因子：
4.4
作者：
Jones, Gareth J.;Wiseman, Jeremy C. D.;Mody, Christopher H.
通讯作者：
Mody, Christopher H.