The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception.
The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception.
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DOI：
10.1016/j.isci.2018.08.007
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发表时间：
2018-08-31
期刊：
影响因子：
5.8
通讯作者：
Tominaga M
中科院分区：
文献类型：
--
作者：
Maruyama K;Takayama Y;Sugisawa E;Yamanoi Y;Yokawa T;Kondo T;Ishibashi KI;Sahoo BR;Takemura N;Mori Y;Kanemaru H;Kumagai Y;Martino MM;Yoshioka Y;Nishijo H;Tanaka H;Sasaki A;Ohno N;Iwakura Y;Moriyama Y;Nomura M;Akira S;Tominaga M
白色念珠菌感染可引起皮肤、外阴或口腔疼痛。尽管白色念珠菌具有明显的镇痛活性，但真菌伤害性的分子机制在很大程度上仍不清楚。在这里，我们展示了白色念珠菌特异的信号通路导致了严重的机械性异位痛觉。我们发现，白念珠菌衍生的β-葡聚糖依赖Dectin-1刺激伤害性感受器，并在炎性疼痛中通过两条途径发挥作用。主要途径通过Dectin-1介导的ATP-P2X3/P2X2/3轴，通过角质形成细胞和初级感觉神经元之间的细胞间联系，依赖于ATP转运体泡核苷酸转运体(VNUT)。另一条通路通过Dectin-1介导的PLC-TRPV1/TRPA1轴在初级感觉神经元中发挥作用。有趣的是，白念珠菌衍生的β-葡聚糖具有增强组胺非依赖性瘙痒的能力，VNUT抑制剂氯屈膦酸盐可用于治疗β-葡聚糖引起的不适感觉。总的来说，这是第一个表明Dectin-1和VNUT介导的检测真菌感染的先天感觉机制的报告。β-葡聚糖诱导的疼痛在Dectin-1和TRPV1/TRPA1基因缺陷小鼠中被消除β-葡聚糖通过Dectin-1-PLC轴刺激伤害性感受器，激活神经元β-葡聚糖诱导的痛觉过敏依赖于细胞外的三磷酸腺苷和VNUT VNUT抑制剂氯膦酸盐可用于治疗β-葡聚糖诱导的痛觉异常行为的分子机制；分子神经科学；医学微生物学
Candida albicans infection can cause skin, vulvar, or oral pain. Despite the obvious algesic activity of C. albicans, the molecular mechanisms of fungal nociception remain largely unknown. Here we show that the C. albicans-specific signaling pathway led to severe mechanical allodynia. We discovered that C. albicans-derived β-glucan stimulated nociceptors depending on Dectin-1, and two pathways in inflammatory pain. The major pathway operates via the Dectin-1-mediated ATP-P2X3/P2X2/3 axis through intercellular relationships between keratinocytes and primary sensory neurons, which depends on the ATP transporter vesicular nucleotide transporter (VNUT). The other pathway operates via the Dectin-1-mediated PLC-TRPV1/TRPA1 axis in primary sensory neurons. Intriguingly, C. albicans-derived β-glucan has the ability to enhance histamine-independent pruritus, and VNUT inhibitor clodronate can be used to treat unpleasant feelings induced by β-glucan. Collectively, this is the first report to indicate that Dectin-1 and VNUT mediated innate sensory mechanisms that detect fungal infection. β-Glucan-induced pain is abolished in Dectin-1- and TRPV1/TRPA1-deficient mice β-–Glucan stimulates nociceptors via Dectin-1-PLC axis, activating neurons β-Glucan-induced allodynia is dependent on extracellular ATP and VNUT VNUT inhibitor clodronate can be used to treat β-glucan-induced allodynia Molecular Mechanism of Behavior; Molecular Neuroscience; Medical Microbiology
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影响因子：
5.4
作者：
Koyanagi, Y;Tanaka, Y;Yamamoto, N
通讯作者：
Yamamoto, N
影响因子：
32.4
作者：
Kashem SW;Riedl MS;Yao C;Honda CN;Vulchanova L;Kaplan DH
通讯作者：
Kaplan DH
DOI：
10.1073/pnas.93.23.13316
发表时间：
1996-11-12
影响因子：
11.1
作者：
Inoue, I;Yanai, K;Watanabe, T
通讯作者：
Watanabe, T
DOI：
10.1073/pnas.252537299
发表时间：
2002-12-24
影响因子：
11.1
作者：
Jarvis, MF;Burgard, EC;Faltynek, C
通讯作者：
Faltynek, C
DOI：
10.1007/s00424-009-0703-x
发表时间：
2009-10
期刊：
Pflugers Archiv : European journal of physiology
影响因子：
--
作者：
Mandadi S;Sokabe T;Shibasaki K;Katanosaka K;Mizuno A;Moqrich A;Patapoutian A;Fukumi-Tominaga T;Mizumura K;Tominaga M
通讯作者：
Tominaga M