Immunologic homeostasis during infection:: Coexistence of strong pulmonary cell-mediated immunity to secondary Cryptococcus neoformans infection while the primary infection still persists at low levels in the lungs
Immunologic homeostasis during infection:: Coexistence of strong pulmonary cell-mediated immunity to secondary Cryptococcus neoformans infection while the primary infection still persists at low levels in the lungs
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DOI：
10.4049/jimmunol.177.7.4652
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Huffnagle, Gary B.
中科院分区：
文献类型：
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作者：
Lindell, Dennis M.;Ballinger, Megan N.;Huffnagle, Gary B.
维持对持久性病原体的免疫力尚不清楚。在这项研究中，我们使用持续肺部真菌感染的小鼠模型来研究正在进行的细胞介导的免疫反应。低水平持续性新型隐球菌感染的CBA/J小鼠肺中存在效应记忆表型的CD4(+) T细胞。虽然不能消除原发感染导致不育，但这些小鼠对新生隐球菌的再次攻击表现出免疫记忆的特征：1)继发性隐球菌攻击得到更快的控制，2)炎症反应的发展和消退更快，3)CD4(+) T和CD8(+) T细胞反应的强度更高，4)T细胞产生的效应细胞因子大大增强。在继发性攻击时，CD4(+) T细胞的消耗会对肺部新生梭状细胞的清除产生不利影响。这些结果表明，持续低水平感染新形梭菌不会损害细胞介导的对真菌的反应。虽然它们相对没有明显的疾病，但如果新生梭状菌的负担增加，这些小鼠可以迅速产生二次免疫反应。这些数据支持这样一个概念，免疫健康的个体可以保持低数量的隐球菌，隐球菌可以成为免疫缺陷状态（如艾滋病）再激活疾病的病灶。
Maintenance of immunity to persistent pathogens is poorly understood. In this study, we used a murine model of persistent pulmonary fungal infection to study the ongoing cell-mediated immune response. CBA/J mice with low-level persistent Cryptococcus neoformans infection had CD4(+) T cells of effector memory phenotype present in their lungs. Although unable to eliminate the primary infection to sterility, these mice displayed hallmarks of immunologic memory in response to rechallenge with C. neoformans: 1) the secondary cryptococcal challenge was controlled much more rapidly, 2) the inflammatory response developed and resolved more rapidly, 3) CD4(+) T and CD8(+) T cell responses were higher in magnitude, and 4) effector cytokine production by T cells was greatly enhanced. Depletion of CD4(+) T cells at the time of secondary challenge adversely affected clearance of C. neoformans from the lungs. These results demonstrate that persistent low-level infection with C. neoformans does not impair the cell-mediated response to the fungus. Although they are relatively free of overt disease, these mice can respond with a rapid secondary immune response if the burden of C. neoformans increases. These data support the concept that immunologically healthy individuals can maintain low numbers of cryptococci that can become a nidus for re-activation disease during immunodeficient states such as AIDS.