Analyses of protection mechanisms against Candida albicans infection in various animal models

不同动物模型对白色念珠菌感染的保护机制分析

• 批准号: 61570202
• 负责人: MIKAMI Yuzuru
• 金额: $ 1.47万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570202/
• 关键词: Candidiasis; mouse infection model; effectors; BRM; amphotericin B; Conbination therapy; レンチナン; レバミゾール; 免疫増強物質; カンジダ感染; 感染防御効果

Although candidiasis is the most commonly observed systemic mycosis in a compromised host, constituting a significant percentage of all infections, the mechanisms of host defense against the infection have not been fully understood. Two major types of defense mechanisms, one non-specific and one-speci-fic, have been considered responsible for the resistance to candidiasis. In this study, firstly it was aimed to develop useful model for the study of fungal infections and analyses of effector cells which play an important defensive role against fungal infections. Secondly, actual analitic studies of various effectors in these newly developed models using various BRMs(biological response modifiers).Throughout the present studies, it was confirmed that intravenous or intraperitoneal infection models in mice is still useful ones for the test of the effectiveness of various BRMs as well as antifungal chemotherapeutics. However, itwas found that in these intravenous or intraperitoneal Candida … More albicans infection models,infection is too early to manifest complicated host defense mechanisms: therefore, those systemic candemia models are not always suitable for studies of the progressive development of host resistance to the infection. The other problem is that when mice are infected with Candida by the i.v. or i.p. route, the organisms grow in the connecting tubles or in the pelvis of the kidneys even after the host defense mechanisms in other organs have fully marshalled their forces to eradicate the Candida cells The host defense against C. albicans is assumed to be diminished in the kidney due to its functional or structural characteristics. However, compared to these progressive candemia models, in mouse thigh lesion model reported by the present studies, a mouse does not die from the infection, and the host defense mechanisms can fully develop and operate without being impaired by other factors. Therefore, this model was considered to be useful for the study histopathological mechanisms of infections. Further studies, however, also indicated that mouse thigh lesion model has also disadvantages and is not suitable for the test of antifungal activity of chemotherapeutic agents, because even amphotericin B, flucytosine or ketoconazole does not exhibited any activities in this model. Our studies using these models also showed the possibilities that different effector cells play an important role in different infection models for the eradication of fungal elements.Active roles of interferons and interleukins produced by BRMs against fungal infections are also confirmed. Less

尽管念珠菌病是感染宿主中最常见的系统性真菌病，在所有感染中占很大比例，但宿主对感染的防御机制尚未完全了解。两种主要类型的防御机制，一种是非特异性的，一种是特异性的，被认为是对念珠菌耐药的原因。在这项研究中，首先旨在为真菌感染的研究和对真菌感染起重要防御作用的效应细胞的分析建立有用的模型。其次，使用不同的生物反应调节剂(BRM)对这些新开发的模型中的各种效应进行了实际分析。通过本研究，证实了小鼠静脉或腹膜感染模型仍然是测试各种BRM以及抗真菌化疗药物有效性的有用模型。然而，人们发现在这些静脉或腹膜腔内的念珠菌…白念珠菌感染模型较多，感染表现出复杂的宿主防御机制还为时过早：因此，这些系统性烛血模型并不总是适合于研究宿主对感染抵抗力的进行性发展。另一个问题是，当小鼠通过静脉注射感染念珠菌时。或者IP。在此过程中，即使在其他器官的宿主防御机制已经充分调动它们的力量来根除念珠菌细胞之后，这些微生物也会在连接的小管或肾脏的盆腔中生长。然而，与这些进行性烛血模型相比，在本研究报道的小鼠大腿病变模型中，小鼠不会死于感染，宿主防御机制可以充分发展和运行，而不受其他因素的影响。因此，该模型被认为对研究感染的组织病理学机制是有用的。然而，进一步的研究也表明，小鼠大腿皮损模型也存在缺陷，不适合用于化疗药物的抗真菌活性测试，因为即使是两性霉素B、氟胞嘧啶或酮康唑在该模型中也没有显示出任何活性。我们使用这些模型的研究还表明，不同的效应细胞可能在不同的感染模式中发挥重要作用，以根除真菌元素。BRM产生的干扰素和白介素A对真菌感染的积极作用也得到证实。较少

项目成果

三上襄他: 医真菌誌. 28. (1987)

Mikami Jo 等人：《医学真菌学杂志》28。（1987）

T. Arai et al.: "Paecilotoxin (leucinostatin), a possible etiological agents for opportunistic fungal infection." Proc. 14th International Congress of Microbiology, IUMS. 1. (1986)

T. Arai 等人：“拟青霉毒素（亮氨抑素），机会性真菌感染的可能病原体。”

T.Arai et al.: Proc.14th International Congress of Microbiology. 1. 155 (1986)

T.Arai 等人：第 14 届国际微生物学大会论文集。

H. -Y. Chen et al.: "Protective effects of various BRMs against Candida albicans infections." Jpn. J.Med Mycol.28. 262-269 (1987)

H.-Y。