Bellocchio S, Bozza S, Montagnoli C, Perruccio K, Gaziano R, Pitzurra L, Romani L
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Med Mycol. 2005 May;43 Suppl 1:S181-8. doi: 10.1080/14789940500051417.
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.
对真菌的有效免疫反应需要不同的免疫机制。树突状细胞（DCs）具有独特的能力来解码与真菌相关的信息，并将其转化为性质不同的辅助性T细胞（Th）免疫反应。小鼠和人类的DCs通过不同的识别受体吞噬烟曲霉的分生孢子和菌丝。不同受体的结合会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刺激。过继转移不同类型的DCs会激活保护性和非保护性的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。输注经真菌脉冲处理或RNA转染的DCs也能加速同种异体造血干细胞移植小鼠功能性抗真菌Th1反应的恢复。接受去除T细胞的同种异体造血干细胞移植的患者，由于DC功能缺陷，在移植后不久无法产生抗原特异性T细胞反应。我们的结果表明，DCs的过继转移可能通过促进T细胞的教育程序来恢复造血干细胞移植中的免疫能力。因此，DCs显著的功能可塑性可被用于针对细胞介导免疫的细胞和途径，以应对真菌。
