Angulo Iñigo, Jiménez-Díaz María Belén, García-Bustos José Francisco, Gargallo Domingo, de las Heras Federico Gómez, Muñoz-Fernández María Angeles, Fresno Manuel
Centro de Biología Molecular, Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Cell Immunol. 2002 Jul-Aug;218(1-2):46-58. doi: 10.1016/s0008-8749(02)00521-x.
Systemic infections caused by fungi after cytoreductive therapies are especially difficult to deal with in spite of currently available antimicrobials. However, little is known about the effects of fungi on the immune system of immunosuppressed hosts. We have addressed this by studying the in vitro T cell responses after systemic infection with Candida albicans in cyclophosphamide-treated mice. After cyclophosphamide treatment, a massive splenic colonization of the spleens, but not lymph nodes, by immature myeloid progenitor (Ly-6G(+)CD11b(+))cells is observed. These cells are able to suppress proliferation of T lymphocytes via a nitric oxide (NO)-dependent mechanism. Systemic infection with a sublethal dose of C. albicans did not cause immunosuppression per se but strongly increased NO-dependent suppression in cyclophosphamide-treated mice, by selective priming of suppressive myeloid progenitors (Ly-6G(+)CD11b(+)CD31(+)CD40(+)WGA(+)CD117(low/-)CD34(low/-)) for iNOS protein expression. The results indicate that systemic C. albicans infection can augment the effects of immunosuppressive therapies by promoting functional changes in immunosuppressive cells.
尽管目前有抗菌药物，但细胞减灭疗法后由真菌引起的全身感染尤其难以处理。然而，关于真菌对免疫抑制宿主免疫系统的影响却知之甚少。我们通过研究环磷酰胺处理的小鼠全身性感染白色念珠菌后的体外T细胞反应来解决这个问题。环磷酰胺处理后，观察到未成熟髓系祖细胞（Ly-6G(+)CD11b(+)）在脾脏而非淋巴结中大量定植。这些细胞能够通过一氧化氮（NO）依赖性机制抑制T淋巴细胞的增殖。用亚致死剂量的白色念珠菌进行全身感染本身并不会导致免疫抑制，但通过选择性启动抑制性髓系祖细胞（Ly-6G(+)CD11b(+)CD31(+)CD40(+)WGA(+)CD117(low/-)CD34(low/-)）的诱导型一氧化氮合酶（iNOS）蛋白表达，在环磷酰胺处理的小鼠中强烈增加了NO依赖性抑制。结果表明，全身性白色念珠菌感染可通过促进免疫抑制细胞的功能变化来增强免疫抑制疗法的效果。
