Low-Density Neutrophil Levels Are Correlated with Sporotrichosis Severity: Insights into Subcutaneous Fungal Infection.

Abstract

Low-density neutrophils (LDNs) constitute a distinct subset of neutrophils among peripheral blood mononuclear cells. They are key mediators in systemic infections, amplifying inflammatory responses and potentially influencing disease severity and chronicity. However, their roles in subcutaneous fungal infections have not been previously investigated. In this study, we observed increased neutrophil counts in the blood and tissues of sporotrichosis patients through automated blood analysis, histology, and immunohistochemistry. Additionally, we found elevated granulocyte colony-stimulating factor (G-CSF) levels by enzyme-linked immunosorbent assays. Flow cytometry analysis revealed a significant increase in CD16+CD66b+ LDNs compared with healthy controls. In vitro stimulation with Sporothrix globosa induced LDN generation. We observed positive correlations of LDN frequency with levels of C-reactive protein and myeloperoxidase. Conversely, G-CSF levels were negatively correlated with LDN frequency. LDNs exhibited a combined mature/immature phenotype. Notably, transcriptomic analysis showed downregulation of anti-inflammatory signaling pathways in LDNs; functional assays also demonstrated reduced phagocytosis, reactive oxygen species production, and neutrophil extracellular trap formation after stimulation with Sporothrix globosa. Degranulation did not exhibit significant changes, suggesting that LDNs constitute an impaired subpopulation. Our findings in the context of subcutaneous fungal infections indicate that LDN levels are significantly elevated in sporotrichosis and positively correlated with disease severity.