Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Laboratório de Micologia Clínica, Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, Câmpus de Araraquara, Universidade Estadual Paulista (UNESP), Araraquara, São Paulo, Brazil.
Curr Top Microbiol Immunol. 2019;422:101-120. doi: 10.1007/82_2018_145.
Cryptococcus neoformans is a human pathogenic yeast that causes hundreds of thousands of deaths worldwide among susceptible individuals, in particular, HIV+ patients. This yeast has developed several adaptation mechanisms that allow replication within the host. During decades, this yeast has been well known for a very peculiar and unique structure that contributes to virulence, a complex polysaccharide capsule that surrounds the cell wall. In contrast to other fungal pathogens, such as Candida albicans or Aspergillus fumigatus, the role of morphological transitions has not been studied in the virulence of Cryptococcus neoformans since this yeast does not form hyphae during infection. However, in the last years, different groups have described the ability of this fungus to change its size during infection. In particular, Cryptococcus can form "titan cells," which are blastoconidia of an abnormal large size. Since their discovery, there is increasing evidence that these cells contribute, not only to long-term persistence in the host, but they can also actively participate in the development of the disease. Recently, several groups have simultaneously described different media that induce the appearance of titan cells in laboratory conditions. Using these conditions, new inducing factors and signaling pathways involved in this transition have been described. In this article, we will review the main phenotypic features of these cells, factors, and transduction pathways that induce cell growth, and how titan cells contribute to the disease caused by this pathogen.
新型隐球菌是一种人类致病性酵母，它会导致全球成千上万的易感个体，特别是 HIV 阳性患者死亡。这种酵母已经发展出几种适应机制，使其能够在宿主内复制。几十年来，这种酵母因其独特而独特的结构而广为人知，这种结构有助于其毒力，即包围细胞壁的复杂多糖荚膜。与其他真菌病原体（如白色念珠菌或烟曲霉）不同，由于这种酵母在感染过程中不形成菌丝，因此其形态转变在新型隐球菌的毒力中的作用尚未得到研究。然而，在过去的几年中，不同的研究小组已经描述了这种真菌在感染过程中改变其大小的能力。特别是，新型隐球菌可以形成“泰坦细胞”，这是一种异常大的芽生孢子。自发现以来，越来越多的证据表明，这些细胞不仅有助于在宿主中长期存活，而且还可以积极参与疾病的发展。最近，几个研究小组同时描述了不同的培养基，可以在实验室条件下诱导泰坦细胞的出现。使用这些条件，已经描述了参与这种转变的新诱导因子和信号转导途径。在本文中，我们将回顾这些细胞的主要表型特征、诱导细胞生长的因子和转导途径，以及泰坦细胞如何导致这种病原体引起的疾病。
