Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2TN, UK.
Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Fungal Genet Biol. 2019 Nov;132:103261. doi: 10.1016/j.fgb.2019.103261. Epub 2019 Aug 12.
Cryptococcus infections represents a major healthcare burden, with over 200,000 cases globally a year and even with treatment, mortality remains as high as 80%. There is a clear need for new classes of treatment, especially with the global threat of antifungal resistance. Several groups are investigating the potential of immunotherapy - circumventing many of the issues with current treatments. Macrophages are a cell type known to be heavily associated with cryptococcal infection, from the innate immune response through to the later stage chronic adaptive response - making these an ideal target for manipulation. However, it is currently debated whether macrophage activity is positive or negative for host outcomes. Here, we discuss the current literature surrounding the role of macrophages during Cryptococcus infection, and makes cases for and against macrophage enhancement. Finally, we discuss which pressing questions in the field still remain that require answers in order to safely design an immunotherapeutic with high efficacy.
隐球菌感染是一个重大的医疗保健负担，全球每年有超过 20 万例病例，即使进行治疗，死亡率仍然高达 80%。显然需要新的治疗类别，特别是在全球抗真菌耐药性的威胁下。许多研究小组正在研究免疫疗法的潜力——避免了当前治疗方法的许多问题。巨噬细胞是一种与隐球菌感染密切相关的细胞类型，从先天免疫反应到后期慢性适应性反应——使这些细胞成为操纵的理想目标。然而，目前对于巨噬细胞的活动对宿主结果是积极的还是消极的仍存在争议。在这里，我们讨论了当前围绕巨噬细胞在隐球菌感染中的作用的文献，并提出了支持和反对增强巨噬细胞的观点。最后，我们讨论了该领域仍存在哪些亟待解决的问题，需要答案才能安全地设计出具有高疗效的免疫疗法。
