Impact of GM-CSF deficiency on the disease course and immune response in mice infected with Exophiala oligosperma
- Author:
DONG Qi
;
LU Jiejie
;
WU Weiwei
- Publication Type:Journal Article
- Keywords:
GM-CSF;
dematiaceous fungi;
Exophiala oligosperma;
innate immune response;
neutrophils
- From:
China Tropical Medicine
2025;25(1):28-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) deficiency in the pathogenesis of Exophiala oligosperma (E. oligosperma) infection, a dematiaceous fungus, aiming to provide new insights and evidence for the treatment of dematiaceous fungal infections. Methods C57BL/6 wild-type (WT) mice and Csf2 gene knockout (KO) mice (C57BL/6 background) were selected. Using E. oligosperma isolated from patients with caspase recruitment domain-containing protein 9 (CARD9) gene deficiency, a murine subcutaneous infection model was established to simulate the human infection route. The natural progression of infection in the mice was observed for six weeks, with skin lesion tissues collected at appropriate time points for pathological analysis and monitoring immune responses. Results Both WT and Csf2 KO mice exhibited spontaneous pathogen clearance and gradual recovery of foot tissue appearance during the progression of infection, with a 100% survival rate at the end of observation. Compared to WT mice, Csf2 KO mice showed reduced footpad swelling at 1 and 2 weeks post-infection (t=4.674, t=5.961, P<0.01). Fungal clearance in Csf2 KO mice was delayed, with fungal colonies still detectable in lesion tissues at week 4, and Periodic Acid-Schiff (PAS)-positive fungal spores observed in histopathological sections. There was no significant difference found in macrophage infiltration between WT and Csf2 KO mice during the early stages of infection (1-2 weeks) (P>0.05), while neutrophil infiltration was significantly reduced in Csf2 KO mice at week 2 (t=3.287, P<0.01). In addition, Csf2 KO mice exhibited lower levels of IL-6 and IL-1β in foot lesion homogenates at week 1 (t=4.686, t=4.102, P<0.05). Conclusions This study demonstrated that GM-CSF deficiency delays pathogenic fungi clearance, prolongs the disease course and affects early inflammatory cytokine production as well as neutrophil infiltration during the early stages of fungal infections.
- Full text:20251113165515634135.Impact of GM-CSF deficiency on the disease course and immune response in mice infected with Exophiala oligosperma.pdf
