Roussey Jonathan A, Olszewski Michal A, Osterholzer John J
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Pulmonary Section, Medical Service, VA Ann Arbor Health System, Ann Arbor, MI 48105, USA.
Microorganisms. 2016 Dec 10;4(4):47. doi: 10.3390/microorganisms4040047.
This review addresses specific regulatory mechanisms involved in the host immune response to fungal organisms. We focus on key cells and regulatory pathways involved in these responses, including a brief overview of their broader function preceding a discussion of their specific relevance to fungal disease. Important cell types discussed include dendritic cells and regulatory T cells, with a focus on specific studies relating to their effects on immune responses to fungi. We highlight the interleukin-10, programmed cell death 1, and cytotoxic T lymphocyte-associated protein 4 signaling pathways and emphasize interrelationships between these pathways and the regulatory functions of dendritic cells and regulatory T cells. Throughout our discussion, we identify selected studies best illustrating the role of these cells and pathways in response to specific fungal pathogens to provide a contextual understanding of the tightly-controlled network of regulatory mechanisms critical to determining the outcome of exposure to fungal pathogens. Lastly, we discuss two unique phenomena relating to immunoregulation, protective tolerance and immune reactivation inflammatory syndrome. These two clinically-relevant conditions provide perspective as to the range of immunoregulatory mechanisms active in response to fungi.
本综述探讨了宿主对真菌生物体免疫反应中涉及的特定调节机制。我们关注这些反应中涉及的关键细胞和调节途径,在讨论它们与真菌疾病的具体相关性之前,先简要概述其更广泛的功能。所讨论的重要细胞类型包括树突状细胞和调节性T细胞,重点是与它们对真菌免疫反应影响相关的具体研究。我们强调白细胞介素-10、程序性细胞死亡1和细胞毒性T淋巴细胞相关蛋白4信号通路,并强调这些通路与树突状细胞和调节性T细胞调节功能之间的相互关系。在整个讨论过程中,我们确定了一些最佳研究,以说明这些细胞和途径在应对特定真菌病原体时的作用,从而对决定接触真菌病原体结果至关重要的严格控制的调节机制网络有一个背景性的理解。最后,我们讨论了与免疫调节相关的两种独特现象,即保护性耐受和免疫重新激活炎症综合征。这两种临床相关情况为应对真菌时活跃的免疫调节机制范围提供了视角。