Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans.
Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans.
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DOI：
10.1038/s41598-021-92991-6
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发表时间：
2021-06-30
影响因子：
4.6
通讯作者：
Wozniak KL
中科院分区：
文献类型：
--
作者：
Nelson BN;Beakley SG;Posey S;Conn B;Maritz E;Seshu J;Wozniak KL
隐球菌性脑膜炎是一种由机会致病真菌新型隐球菌引起的免疫功能低下的疾病。以前的研究表明，真菌被树突状细胞（DC）吞噬，并被运输到溶酶体，在那里它被氧化和非氧化机制杀死。虽然来自溶酶体的某些分子已知可以杀死或抑制C。在新生动物中，溶酶体是一种含有许多不同蛋白质和酶的细胞器，其被设计为降解吞噬的物质。我们推测，多种溶酶体成分，包括半胱氨酸蛋白酶和抗菌肽，可以抑制C。新人类我们的研究确定了DC溶酶体的内容物，并检查了溶酶体内发现的不同蛋白质的抗隐球菌特性。结果表明，几种树突状细胞溶酶体蛋白影响C.体外培养的新生儿。杀死或抑制真菌的蛋白质以剂量依赖的方式这样做。此外，发现隐球菌抑制所需的蛋白质浓度对哺乳动物细胞无细胞毒性。这些数据表明，许多DC溶酶体蛋白具有抗真菌活性，并具有作为基于免疫的治疗剂的潜力。
Cryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.
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影响因子：
2.9
作者：
Cordeiro, Rossana A.;Teixeira, Carlos E. C.;Rocha, Marcos F. G.
通讯作者：
Rocha, Marcos F. G.
影响因子：
3.4
作者：
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Embgenbroich M;Burgdorf S
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