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[模式识别受体对新型隐球菌的识别及其在宿主抵御该感染中的作用]

[Recognition of Cryptococcus neoformans by Pattern Recognition Receptors and its Role in Host Defense to This Infection].

作者信息

Sato Ko, Kawakami Kazuyoshi

机构信息

Department of Medical Microbiology, Mycology and Immunology,Tohoku University Graduate School of Medicine.

Virus Research Center, Clinical Research Division, Sendai Medical Center.

出版信息

Med Mycol J. 2017;58(3):J83-J90. doi: 10.3314/mmj.17.011.

Abstract

Cryptococcus neoformans is a yeast-type opportunistic fungal pathogen with a capsule structure consisting of polysaccharides, such as glucuronoxylomannan and galactoxylomannan, and infects the lungs via an air-borne route. Most healthy individuals undergo asymptomatic infection with granulomatous lesions in the lungs caused by C. neoformans. However, immunocompromised hosts with severely impaired cellular immunity, such as those with acquired immune deficiency syndrome (AIDS), often suffer from disseminated infection into the central nervous system, leading to life-threatening meningoencephalitis. The recognition of pathogen-associated molecular patterns (PAMPs) by macrophages and dendritic cells plays an important role as the first line of host defense in the elimination of pathogens. Recently, numerous pattern recognition receptors (PRRs) that recognize these PAMPs have been identified. Also, the involvement of these PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs), in cryptococcal infection has been analyzed. In particular, TLR9, NLR family pyrin domain-containing 3 (NLRP3), Dectin-2, mannose receptor (MR), and DC-SIGN have been found to recognize the DNA, cell wall components, intracellular polysaccharides, and mannoproteins, respectively. Future studies are expected to promote elucidation of the mechanisms of host immune response to C. neoformans, which will lead to the development of new vaccines and therapies for cryptococcal infection.

摘要

新型隐球菌是一种酵母型机会性真菌病原体,具有由葡糖醛酸木聚糖和半乳糖木聚糖等多糖组成的荚膜结构,通过空气传播途径感染肺部。大多数健康个体感染新型隐球菌后会在肺部形成肉芽肿性病变,但无症状。然而,细胞免疫严重受损的免疫功能低下宿主,如获得性免疫缺陷综合征(AIDS)患者,常常会发生播散性感染,累及中枢神经系统,导致危及生命的脑膜脑炎。巨噬细胞和树突状细胞对病原体相关分子模式(PAMPs)的识别作为宿主防御病原体的第一道防线起着重要作用。最近,已鉴定出许多识别这些PAMPs的模式识别受体(PRRs)。此外,还分析了这些PRRs,如Toll样受体(TLRs)、NOD样受体(NLRs)和C型凝集素受体(CLRs)在隐球菌感染中的作用。特别是,已发现TLR9、含NLR家族pyrin结构域3(NLRP3)、Dectin-2、甘露糖受体(MR)和DC-SIGN分别识别DNA、细胞壁成分、细胞内多糖和甘露糖蛋白。未来的研究有望促进对宿主针对新型隐球菌免疫反应机制的阐明,这将推动新型隐球菌感染疫苗和治疗方法的开发。

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