Immunity to Aspergillus fumigatus:: the basis for immunotherapy and vaccination
Immunity to Aspergillus fumigatus:: the basis for immunotherapy and vaccination
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DOI：
10.1080/14789940500051417
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发表时间：
2005-05-01
期刊：
影响因子：
2.9
通讯作者：
Romani, L
中科院分区：
文献类型：
--
作者：
Bellocchio, S;Bozza, S;Romani, L
对真菌的有效反应需要不同的免疫机制。树突状细胞(DC)是唯一能够解码真菌相关信息并将其转化为本质上不同的T辅助细胞(Th)免疫反应的细胞。小鼠和人树突状细胞通过不同识别受体吞噬烟曲霉分生孢子和菌丝。不同受体的参与转化为不同的下游信号事件，最终影响细胞因子的产生和共同刺激。过继转移不同类型的DC会激活保护性和非保护性Th细胞以及调节性T细胞，最终影响侵袭性曲霉病小鼠的感染结局。在异基因造血干细胞移植的小鼠中，输入真菌冲击或RNA转基因的树突状细胞也加速了功能性抗真菌Th1反应的恢复。由于DC功能缺陷，接受T细胞耗尽异基因造血干细胞移植的患者在移植后不久就无法产生抗原特异性T细胞反应。我们的结果提示，过继转移DC可能通过促进T细胞的培养而恢复造血干细胞移植的免疫活性。因此，树突状细胞显著的细胞可塑性可以被用来刻意地靶向细胞和细胞免疫途径，以响应真菌。
Efficient responses to fungi require different mechanisms of immunity. Dendritic cells (DCs) are uniquely able to decode the fungus-associated information and translate it Into qualitatively different T helper (Th) immune responses. Murine and human DCs phagocytose conidia and hyphae of Aspergillus fumigatus through distinct recognition receptors. The engagement of distinct receptors translates into disparate downstream signaling events, ultimately affecting cytokine production and co-stimulation. Adoptive transfer of different types of DCs activates protective and non-protective Th cells as well as regulatory T cells, ultimately affecting the outcome of the infection in mice with invasive aspergillosis. The infusion of fungus-pulsed or RNA-transfected DCs also accelerates recovery of functional antifungal Th 1 responses in mice with allogeneic hematopoietic stem cell transplantation. Patients receiving T cell-depleted allogeneic hematopoietic stem cell transplantation are unable to develop antigen-specific T cell responses soon after transplant due to defective DC functions. Our results suggest that the adoptive transfer of DCs may restore immunocompetence in hematopoietic stem cell transplantation by contributing to the educational program of T cells. Thus, the remarkable furictional plasticity of DCs can be exploited for the deliberate targeting of cells and pathways of cell-mediated immunity in response to the fungus.