Deslauriers N, Côté L, Montplaisir S, de Repentigny L
Faculty of Dental Medicine, Laval University, Quebec, Canada.
Infect Immun. 1997 Feb;65(2):661-7. doi: 10.1128/iai.65.2.661-667.1997.
Oral candidiasis is a common fungal infection in patients infected with the human immunodeficiency virus (HIV). Although rare at the time of primary HIV infection, it is frequently found throughout the asymptomatic phase and is predictive of progressive immunodeficiency. However, the precise immune defect which results in outgrowth of commensal Candida albicans in HIV infection has not been identified. Mice infected with the Du5H(G6T2) mixture of mouse leukemia viruses develop a syndrome, designated murine AIDS (MAIDS), that has many of the immune abnormalities found in HIV infection. Retrovirus-infected C57BL/6 mice were examined for their ability to resist the development of oral candidiasis from the carrier state established after a self-limiting acute infection and to clear a subsequent secondary inoculum of oral C. albicans. Most of the mice orally colonized with C. albicans and then inoculated with the retrovirus mixture maintained a low-level oral carriage of C. albicans, while 30% of coinfected mice developed recurring 2- to 3-week episodes of acute Candida proliferation, separated by transient recoveries to the carrier state. The frequencies of CD4+ and CD8+ lymphocytes were, respectively, unchanged and significantly decreased (P < 0.05) in both cervical lymph nodes and spleens of coinfected mice compared to the corresponding frequencies in C. albicans-carrying, virus-free, age-matched control animals. Secretion of gamma interferon by concanavalin A (ConA)-stimulated spleen cells from Candida-carrying, retrovirus-infected mice was significantly decreased (P < 0.05) compared to that of C. albicans-carrying, retrovirus-free mice, in accordance with known abnormalities associated with MAIDS. However, production of this cytokine by ConA-stimulated or unstimulated cervical lymph node cells from coinfected mice was enhanced compared to that of virus-free animals colonized with C. albicans. Acquired resistance to reinfection with C. albicans was maintained in retrovirus-infected mice and was associated with a mucosal recruitment of CD8+ cells not observed in control mice. These results suggest that alterations in mucosal immunity which occur in MAIDS differ substantially from defects observed at other sites and that surrogate epithelial defense mechanisms may function locally to limit Candida proliferation.
口腔念珠菌病是人类免疫缺陷病毒（HIV）感染者中常见的真菌感染。虽然在原发性HIV感染时罕见，但在整个无症状期经常出现，并且预示着免疫缺陷的进展。然而，导致HIV感染时共生白色念珠菌生长的精确免疫缺陷尚未明确。感染小鼠白血病病毒Du5H（G6T2）混合物的小鼠会出现一种综合征，称为鼠艾滋病（MAIDS），其具有许多在HIV感染中发现的免疫异常。对逆转录病毒感染的C57BL/6小鼠进行了检查，以评估它们从自限性急性感染后建立的携带状态抵抗口腔念珠菌病发展的能力，以及清除随后口腔白色念珠菌二次接种物的能力。大多数口服定殖白色念珠菌然后接种逆转录病毒混合物的小鼠维持白色念珠菌的低水平口腔携带，而30%的共感染小鼠出现反复的2至3周急性念珠菌增殖发作，期间有短暂恢复到携带状态。与携带白色念珠菌、无病毒、年龄匹配的对照动物相应频率相比，共感染小鼠的颈部淋巴结和脾脏中CD4+和CD8+淋巴细胞频率分别未改变和显著降低（P<0.05）。与携带白色念珠菌、无逆转录病毒的小鼠相比，来自携带念珠菌、逆转录病毒感染小鼠的伴刀豆球蛋白A（ConA）刺激的脾细胞分泌的γ干扰素显著降低（P<0.05），这与已知的与MAIDS相关的异常一致。然而，与定殖白色念珠菌的无病毒动物相比，共感染小鼠的ConA刺激或未刺激的颈部淋巴结细胞产生的这种细胞因子有所增强。逆转录病毒感染的小鼠维持了对白色念珠菌再感染的获得性抵抗力，并且与对照小鼠未观察到的CD8+细胞向黏膜募集有关。这些结果表明，MAIDS中发生的黏膜免疫改变与在其他部位观察到的缺陷有很大不同，并且替代上皮防御机制可能在局部起作用以限制念珠菌增殖。
