ALA-PDT对单癣菌感染小鼠足垫模型的影响及其体内机制。

IF 3.1 3区医学 Q2 ONCOLOGY

Photodiagnosis and Photodynamic Therapy Pub Date : 2025-02-01 DOI:10.1016/j.pdpdt.2024.104452

Xuelin Wu , Wenyi Chen , Muhammad Danish Yaqoob , Kangxing Liu , Yanqing Hu , Yan Lu , Yongxuan Hu

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引用次数: 0

摘要

背景：5-氨基乙酰丙酸光动力疗法（ALA-PDT）在治疗成色菌病（CBM）方面受到越来越多的关注，并在少数临床病例报告中显示出疗效。然而，关于ALA-PDT在小鼠感染模型中对单癣菌的作用及其机制的研究尚不充分。本研究在体内研究了这些问题。方法：采用足垫接种单念珠菌感染小鼠模型。研究了足垫体积、组织真菌负荷和组织病理学特征的变化，以确定ALA-PDT的疗效。在基因和蛋白水平上进一步评估清除者受体MARCO（巨噬细胞胶原结构受体）。采用酶联免疫吸附法检测血清细胞因子TNF-α、GM-CSF、IL-4和IL-10，以指示PDT后免疫微环境的变化。结果：ALA-PDT在体内减少了感染足垫体积、真菌负荷和病理性炎症浸润。在小鼠感染模型中也增加了Marco的表达。此外，PDT上调小鼠血清抗炎因子IL-4和IL-10，下调促炎因子TNF-α和GM-CSF。结论：ALA-PDT对小鼠足垫单孢菌感染模型具有一定的杀真菌作用，可减轻炎症反应。它也可能通过巨噬细胞受体MARCO和调节免疫微环境来帮助宿主对抗细胞内真菌。本研究为ALA-PDT作为一种有前景的辅助治疗方式的方案选择提供了科学依据。

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Effects of ALA-PDT on the murine footpad model of Fonsecaea monophora infection and its related mechanisms in vivo

Background

: 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has received growing attention for treating chromoblastomycosis (CBM) and has shown efficacy in a handful of clinical case reports. However, there is insufficient information regarding the effects of ALA-PDT on Fonsecaea monophora in mouse infection model and the related mechanisms. This study investigated these issues in vivo.

Methods

: A F. monophora infection mouse model inoculated in footpads was used. Changes in the footpad volume, tissue fungal burden, and histopathological characteristics were investigated to determine the efficacy of ALA-PDT. Scavenger receptor MARCO (Macrophage receptor with collagenous structure) was further evaluated at the gene and protein levels. Serum cytokines TNF-α, GM-CSF, IL-4, and IL-10 were measured using enzyme-linked immunosorbent assay to indicate changes in the immune microenvironment after PDT.

Results

: ALA-PDT reduced infected footpad volume, fungal burden, and pathological inflammatory infiltration in vivo. It also increased the expression of Marco in the murine infection model. Furthermore, PDT upregulated the anti-inflammatory cytokines IL-4 and IL-10 while downregulated the pro-inflammatory cytokines TNF-α and GM-CSF in mouse serum.

Conclusions

: ALA-PDT demonstrated fungicidal effects in a mouse footpad infection model with F. monophora and attenuated the inflammatory reactions. It may also assist against the intracellular fungi by the host through macrophage receptor MARCO and regulation of the immune microenvironment. This study provides scientific evidence for the protocol selection of ALA-PDT as a promising adjunctive modality for treating chromoblastomycosis.

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来源期刊

Photodiagnosis and Photodynamic Therapy ONCOLOGY-

CiteScore

5.80

自引率

24.20%

发文量

509

审稿时长

50 days

期刊介绍： Photodiagnosis and Photodynamic Therapy is an international journal for the dissemination of scientific knowledge and clinical developments of Photodiagnosis and Photodynamic Therapy in all medical specialties. The journal publishes original articles, review articles, case presentations, "how-to-do-it" articles, Letters to the Editor, short communications and relevant images with short descriptions. All submitted material is subject to a strict peer-review process.