ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1662183
The Power of GM-CSF: Immune Regulation in the Defense Against Phialophora verrucosa Infection
Provisionally accepted
- 1Third Hospital of Shanxi Medical University, Taiyuan, China
- 2Affiliated Dermatology Hospital of Hainan Medical University, Haikou, China, Haikou, China
- 3The Fifth People's Hospital of Hainan Province, Haikou, China
- 4Shanxi Bethune Hospital, Taiyuan, China
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Background: Phialophora verrucosa, a dematiaceous fungus, causes serious infections such as phaeohyphomycosis. These infections can severely impair patient quality of life and may be life-threatening. Current understanding of host immune defenses against this pathogen remains limited. Objective: This study aims to investigate the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in host defense against P. verrucosa. Using both in vivo and in vitro models, the current study specifically examines how GM-CSF deficiency impacts immune responses and fungal clearance. Methods: C57BL/6 wild-type (WT) and GM-CSF-deficient (Csf2 KO) mice were infected subcutaneously in the footpad with live P. verrucosa conidia. Skin lesion appearance and foot swelling were monitored for 4 weeks. At specific time points, footpad tissues were collected for PAS, CD68, and MPO staining, and colony-forming units were calculated to assess fungal load. Serum and tissue homogenates were analyzed for cytokine levels. Bone marrow-derived macrophages and neutrophils were isolated to evaluate GM-CSF' s impact on chemotaxis, phagocytosis, and killing functions. Results: Compared to WT mice, GM-CSF deficiency significantly delayed fungal clearance and prolonged disease progression, accompanied by reduced inflammatory responses and decreased neutrophil infiltration. In vitro, GM-CSF supplementation restored macrophage chemotaxis and enhanced neutrophil phagocytic activity, but did not affect their killing efficiency. A compensatory increase in IFN-γ levels in Csf2 KO mice was insufficient to overcome the immune defects caused by GM-CSF deficiency. This is a provisional file, not the final typeset article Conclusion: This study reveals the indispensable role of GM-CSF in antifungal immunity and its potential as a therapeutic target for controlling infections caused by dematiaceous fungi.
Keywords: GM-CSF, Phialophora verrucosa, immune response, Neutrophils, Macrophages
Received: 08 Jul 2025; Accepted: 07 Oct 2025.
Copyright: © 2025 Dong, Lu, Liu, WU, Kang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuying Kang, kangyuying@sxbqeh.com.cn
Ruijun Zhang, zhangruijun@sxbqeh.com.cn
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