Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120 Thailand; Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani 12120 Thailand.
Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani 12120 Thailand.
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113259. doi: 10.1016/j.intimp.2024.113259. Epub 2024 Sep 27.
Cryptococcosis, caused by infections with C. neoformans and C. gattii, presents a serious threat to global health and necessitates effective treatment strategies. Granulocyte-Macrophage Colony-Stimulating Factor, GM-CSF, is an immune-modulating cytokine that has been utilized clinically to improve host defense against infection; however, the impact of GM-CSF treatment in C. gattii infection has not been elucidated. Our current study aimed to investigate the effect of GM-CSF treatment on pulmonary immune response during C. gattii infection. In response to C. gattii infection, GM-CSF-expressing T helper cells and CD11b myeloid were enhanced in the lungs. The intranasal administration of GM-CSF during C. gattii infection significantly reduced pulmonary cryptococcal load, promoted an increase in pulmonary Th17 cells, as well as neutrophil infiltration in the lungs. Exposure of neutrophils to C. gattii in the presence of GM-CSF resulted in an increased neutrophil phagocytosis and fungal killing capacity, generation of reactive oxygen species (ROS), and upregulation of inflammatory cytokines and anti-microbial peptides. Although GM-CSF treatment in C. neoformans-infected mice had a comparable impact on the reduction of lung fungal burden, it resulted in the enhancement of Th1-type cytokine IFN-γ and the activation of M1 macrophages. Altogether, this study demonstrated that the intranasal delivery of GM-CSF has distinct effects on promoting the protection against C. gattii and C. neoformans by activating neutrophil/type-17 immune response and stimulating M1 macrophage/type-1 immunity, respectively.
隐球菌病由新型隐球菌和格特隐球菌感染引起，对全球健康构成严重威胁，需要有效的治疗策略。粒细胞-巨噬细胞集落刺激因子（GM-CSF）是一种免疫调节细胞因子，已在临床上用于提高宿主对感染的防御能力；然而，GM-CSF 治疗在格特隐球菌感染中的影响尚未阐明。本研究旨在探讨 GM-CSF 治疗对格特隐球菌感染时肺部免疫反应的影响。在格特隐球菌感染时，GM-CSF 表达的辅助性 T 细胞和 CD11b 髓样细胞在肺部增强。在格特隐球菌感染期间鼻内给予 GM-CSF 可显著降低肺部隐球菌负荷，促进肺部 Th17 细胞增加以及中性粒细胞浸润肺部。在 GM-CSF 存在的情况下，中性粒细胞暴露于格特隐球菌会导致中性粒细胞吞噬和真菌杀伤能力增强、活性氧（ROS）生成增加以及促炎细胞因子和抗微生物肽上调。尽管 GM-CSF 治疗在新型隐球菌感染的小鼠中对降低肺部真菌负荷具有相似的影响，但它导致 Th1 型细胞因子 IFN-γ 的增强和 M1 巨噬细胞的激活。总之，这项研究表明，鼻内给予 GM-CSF 通过激活中性粒细胞/17 型免疫反应和刺激 M1 巨噬细胞/1 型免疫分别对促进格特隐球菌和新型隐球菌的保护具有不同的作用。
