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

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

doi:10.1016/j.pdpdt.2024.104452

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

Photodiagnosis Photodyn Ther. 2024 Dec 20:104452. doi: 10.1016/j.pdpdt.2024.104452. Online ahead of print.

Authors

Xuelin Wu¹, Wenyi Chen², Muhammad Danish Yaqoob², Kangxing Liu², Yanqing Hu², Yan Lu², Yongxuan Hu³

Affiliations

¹ Department of Dermatology and Venereology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China; Department of Dermatology and Venereology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
² Department of Dermatology and Venereology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China.
³ Department of Dermatology and Venereology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China. Electronic address: huyongxuan2003@163.com.

PMID: 39710217
DOI: 10.1016/j.pdpdt.2024.104452

Abstract

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.

Keywords: 5-aminolevulinic acid; Fonsecaea monophora; Photodynamic therapy; chromoblastomycosis; macrophage receptor with collagenous structure; murine model.