Early Human Neutrophil Response to Different Morphotypes of <i>Candida albicans</i> Compared to Bacterial Pathogens

Neutrophils are among the first immune cells recruited during the critical early phase of infection; yet their reaction to Candida albicans morphotypes is not fully defined. Here, we aimed to investigate early neutrophil responses to C. albicans morphotypes compared to bacteria. Freshly isolated human neutrophils were incubated with heat-killed C. albicans, live C. albicans, Escherichia coli, and Staphylococcus aureus as bacterial comparisons for 30 min, 1 h, and 4 h. Afterward, neutrophil activation was assessed via gene expression of neutrophil elastase (ELANE) and myeloperoxidase (MPO), CD66b/CD11b surface marker expression, microbicidal activity, and cytokine release, including IL-22, IL-17A, IL-1ɑ, IL-1β, TNF-ɑ, and IL-6. Neutrophil response pathways were significantly more activated by hyphal C. albicans than HK C. albicans, E.coli, and S. aureus, including the highest MPO and ELANE expression within the first 4 h, compared to heat-killed C. albicans and bacteria. CD66b expression significantly upregulated at 1 h in response to hyphal C. albicans. Neutrophils exhibited a 68% candidacidal effect at 1 h. IL-22 peaked at 1 h and remained elevated; heat-killed C. albicans induced IL-22 and IL-17A at 4 h. Neutrophils show stronger early responses against C. albicans morphotypes compared to E. coli and S. aureus, particularly within 1 h.