COMPARISON OF IMMUNOSUPPRESSIVE EFFECTS OF CYCLOSPORINE-A IN A MURINE MODEL OF SYSTEMIC CANDIDIASIS AND OF LOCALIZED THRUSHLIKE LESIONS
COMPARISON OF IMMUNOSUPPRESSIVE EFFECTS OF CYCLOSPORINE-A IN A MURINE MODEL OF SYSTEMIC CANDIDIASIS AND OF LOCALIZED THRUSHLIKE LESIONS
复制标题
DOI：
10.1128/iai.57.11.3472-3478.1989
复制
发表时间：
1989-11-01
影响因子：
3.1
通讯作者：
SCHAFFNER, A
中科院分区：
文献类型：
--
作者：
KRAUSE, MW;SCHAFFNER, A
白色念珠菌是一种机会性人类病原体，优先在吞噬细胞防御缺陷的患者中引起侵袭性和播散性感染，在 T 细胞功能缺陷的患者中引起严重的皮肤粘膜感染。即使在缺乏适应性免疫机制的情况下，吞噬细胞似乎也能保护宿主免受真菌侵袭，而尚未确定的 T 细胞依赖性因子似乎对于控制体表白色念珠菌是必要的。为了研究宿主在体表的防御机制，我们在小鼠人工气化囊肿中开发了一种新的鹅口疮模型。环孢菌素 A 是 T 细胞介导的免疫和自然杀伤细胞活性的相对选择性抑制剂，促进包囊表面画眉样病变的形成，并阻碍从此类病变中消除白色念珠菌。正如由于不存在抗菌吞噬活性受损所预期的那样，环孢菌素 A 对静脉接种引起的全身性念珠菌病没有影响。 令人惊讶的是，无胸腺裸鼠并不比对照小鼠更容易受到浅表念珠菌病的影响，并且同样受到环孢菌素A的影响。相反，米色小鼠除了吞噬功能障碍外，自然杀伤细胞活性也降低，更容易受到鹅口疮样病变的影响，环孢菌素A在该小鼠品系中的活性相应较低。环孢菌素 A 的免疫抑制会影响宿主防御机制，该机制可有效对抗浅表念珠菌病，但在抵抗这种真菌病的侵袭性形式方面似乎是多余的，这表明宿主针对两种形式的念珠菌病的防御性质不同。
Candida albicans is an opportunistic human pathogen preferentially causing invasive and disseminated infection in patients with defective phagocytic defenses and serious mucocutaneous infection in patients with deficient T-cell function. Phagocytes appear to protect the host from fungal invasion even in the absence of adaptive immune mechanisms, while as-yet-undefined T-cell-dependent factors seem necessary for control of C. albicans on body surfaces. To study host defense mechanisms on body surfaces, we developed a new model of thrush in artificial pneumatized cysts in mice. Cyclosporine A, relative selective suppressor of T-cell-mediated immunity and natural killer cell activity, promoted the formation of thrushlike lesions on cyst surfaces and impeded elimination of C. albicans from such lesions. As expected from the absence of an impairment of antimicrobial phagocytic activity, cyclosporine A had no effect on systemic candidiasis induced by intravenous inoculation. Surprisingly, athymic nude mice were not more susceptible to superficial candidiasis than control mice and were comparably affected by cyclosporine A. In contrast, beige mice, which in addition to phagocytic dysfunction have reduced natural killer cell activity, were more susceptible to thrushlike lesions, and cyclosporine A was correspondingly less active in this mouse strain. Immunosuppression with cyclosporine A affects host defense mechanisms which are operative against superficial candidiasis but appear superfluous in resistance to the invasive form of this mycosis, an indication for the divergent nature of host defense against the two forms of candidiasis.