Inhibition of myeloid-derived suppressor cell arginase-1 production enhances T-cell-based immunotherapy against Cryptococcus neoformans infection.
Inhibition of myeloid-derived suppressor cell arginase-1 production enhances T-cell-based immunotherapy against Cryptococcus neoformans infection.
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抑制骨髓源性抑制细胞精氨酸酶 1 的产生可增强基于 T 细胞的针对新型隐球菌感染的免疫疗法
DOI：
10.1038/s41467-022-31723-4
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发表时间：
2022-07-14
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
隐球菌病是一种潜在的致命性疾病，主要由真菌新型隐球菌引起，隐球菌病的治疗选择是有限的。在这里，我们展示了葡萄糖醛酸甘露聚糖，C。新型球菌诱导小鼠和隐球菌病患者中性粒细胞骨髓来源抑制细胞的募集。消耗嗜中性粒细胞来源的抑制细胞增强宿主对C.新生儿感染。我们确定C型凝集素受体-2d识别葡糖醛酸甘露聚糖，通过启动p38介导的抑制T细胞介导的抗真菌反应的酶β-内酰胺酶-1的产生，增强嗜中性粒细胞来源的抑制细胞的免疫抑制活性。值得注意的是，通过p38的特异性抑制剂SB 202190或口服可利用的受体酪氨酸激酶抑制剂凡德他尼药理学抑制抗真菌酶-1表达，显著增强T细胞介导的抗隐球菌病的抗真菌反应。这些数据揭示了在隐球菌病期间嗜中性粒细胞衍生的抑制细胞的关键抑制作用，并突出了通过抑制抗真菌酶-1的产生来对抗感染性疾病的有希望的免疫学应用。
Cryptococcosis is a potentially lethal disease that is primarily caused by the fungus Cryptococcus neoformans, treatment options for cryptococcosis are limited. Here, we show glucuronoxylomannan, the major polysaccharide component of C. neoformans, induces the recruitment of neutrophilic myeloid-derived suppressor cells in mice and patients with cryptococcosis. Depletion of neutrophilic myeloid-derived suppressor cells enhances host defense against C. neoformans infection. We identify C-type lectin receptor-2d recognizes glucuronoxylomannan to potentiate the immunosuppressive activity of neutrophilic myeloid-derived suppressor cells by initiating p38-mediated production of the enzyme arginase-1, which inhibits T-cell mediated antifungal responses. Notably, pharmacological inhibition of arginase-1 expression by a specific inhibitor of p38, SB202190, or an orally available receptor tyrosine kinase inhibitor, vandetanib, significantly enhances T-cell mediated antifungal responses against cryptococcosis. These data reveal a crucial suppressive role of neutrophilic myeloid-derived suppressor cells during cryptococcosis and highlight a promising immunotherapeutic application by inhibiting arginase-1 production to combat infectious diseases.
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影响因子：
32.4
作者：
Lai, Jiann-Jyh;Cruz, Freidrich M.;Rock, Kenneth L.
通讯作者：
Rock, Kenneth L.
影响因子：
3.1
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MODY, CH;SYME, RM
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SYME, RM
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2.6
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Nakamura, Kiwamu;Kinjo, Takeshi;Kawakami, Kazuyoshi
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Kawakami, Kazuyoshi
影响因子：
4.4
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Aldemir, H;Prod'homme, V;Braud, VM
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Braud, VM
影响因子：
7.3
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Abdissa K;Nerlich A;Beineke A;Ruangkiattikul N;Pawar V;Heise U;Janze N;Falk C;Bruder D;Schleicher U;Bogdan C;Weiss S;Goethe R
通讯作者：
Goethe R