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

虽然念珠菌病是最常见的全身性真菌病，在所有感染中占很大比例，但宿主防御感染的机制尚未完全了解。两种主要类型的防御机制，一种非特异性和一种特异性，被认为对念珠菌病的抗性负责。本研究首先为真菌感染的研究和分析在真菌感染中起重要防御作用的效应细胞建立有用的模型。其次，利用各种生物反应调节剂对这些新开发模型中的各种效应物进行实际分析研究。通过本研究证实，小鼠静脉或腹腔感染模型仍然是检验各种BRMs和抗真菌化疗药物有效性的有效模型。然而，我们发现在这些静脉或腹腔念珠菌较多的白色念珠菌感染模型中，感染时间太早，无法表现出复杂的宿主防御机制，因此，这些全体性念珠菌模型并不总是适合于研究宿主对感染抵抗的进展性发展。另一个问题是，当小鼠通过静脉注射或i.p.途径感染念珠菌时，即使在其他器官的宿主防御机制完全集结力量消灭念珠菌细胞之后，生物体仍在肾脏的连接管或骨盆中生长。由于其功能或结构特征，宿主对白色念珠菌的防御被认为在肾脏中减弱。然而，与这些进行性念母菌模型相比，在本研究报道的小鼠大腿病变模型中，小鼠不会因感染而死亡，宿主防御机制可以完全发育和运作，而不会受到其他因素的损害。因此，该模型被认为对研究感染的组织病理学机制有用。然而，进一步的研究也表明，小鼠大腿病变模型也有缺点，不适合用于化疗药物抗真菌活性的测试，因为即使两性霉素B、氟胞嘧啶或酮康唑在该模型中也没有表现出任何活性。我们利用这些模型的研究也表明，不同的效应细胞在不同的感染模型中对真菌元素的根除起着重要的作用。BRMs产生的干扰素和白细胞介素对真菌感染也有积极作用。少

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