Claudia Montagnoli, Bacci Angela, Silvia Bozza, Gaziano Roberta, Spreca Antonio, Romani Luigina
Department of Experimental Medicine and Biochemical Sciences, Medical School, University of Perugia, Italy.
Curr Mol Med. 2002 Sep;2(6):507-24. doi: 10.2174/1566524023362203.
Human beings are continuously exposed to fungi, yet they rarely get fungal diseases. The delicate balance between the host and these otherwise harmless pathogens may turn into a parasitic relationship, resulting in the development of severe infections. The ability to reversibly switch between unicellular and filamentous forms, all of which can be found in infected tissues, is thought to be important for virulence. Efficient responses to the different forms of fungi require different mechanisms of immunity. Dendritic cells (DC) are uniquely able at decoding the fungus-associated information and translating it in qualitatively different T helper (Th) immune responses, in vitro and in vivo. Myeloid DC phagocytosed yeasts and hyphae of Candida albicans and conidia and hyphae of Aspergillus fumigatus, both in vitro and in vivo. Phagocytosis occurred through distinct phagocytic morphologies, involving the engagement and cooperativity of distinct recognition receptors. However, receptor engagement and cooperativity were greatly modified by opsonization. The engagement of distinct receptors translated into disparate downstream signaling events, ultimately affecting cytokine production and costimulation. In vivo studies confirmed that the choice of receptor and mode of entry of fungi into DC was responsible for Th polarization and patterns of susceptibility or resistance to infection. Adoptive transfer of different types of DC activated protective, nonprotective and regulatory T cells, ultimately affecting the outcome of infection. The conclusions are that the selective exploitation of receptors and mode of entry into DC may determine the full range of host's immune relationships with fungi and have important implications in the design of vaccine-based strategies.
人类持续接触真菌，但很少患上真菌疾病。宿主与这些原本无害的病原体之间微妙的平衡可能会转变为寄生关系，导致严重感染的发生。真菌能够在单细胞和丝状形式之间可逆转换，而这两种形式都能在感染组织中找到，这种能力被认为对其毒力很重要。针对不同形式真菌的有效反应需要不同的免疫机制。树突状细胞（DC）在体外和体内都具有独特的能力，能够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（Th）免疫反应。髓样DC在体外和体内都能吞噬白色念珠菌的酵母和菌丝以及烟曲霉的分生孢子和菌丝。吞噬作用通过不同的吞噬形态发生，涉及不同识别受体的参与和协同作用。然而，受体的参与和协同作用会因调理作用而发生很大改变。不同受体的参与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。体内研究证实，真菌进入DC所选择的受体和方式决定了Th极化以及对感染的易感性或抵抗力模式。不同类型DC的过继转移激活了保护性、非保护性和调节性T细胞，最终影响感染的结果。结论是，对受体的选择性利用以及进入DC的方式可能决定宿主与真菌的全部免疫关系，并对基于疫苗的策略设计具有重要意义。
