Graduate student Sungkyunkwan Univ., United States
Disclosure(s):
Hyeon Jin Cho: No financial relationships to disclose
Introduction/Rationale: Opportunistic fungi such as Candida glabrata cause severe, drug-resistant infections in immunocompromised patients. Neutrophils are key to controlling candidiasis, but C. glabrata can evade their defenses. Enhancing neutrophil activity may therefore provide therapeutic benefit. The formyl peptide receptor (FPR) family, highly expressed in neutrophils, regulates their activation, but its role in fungal infection remains unclear. Here, we investigated whether the FPR2 agonist WKYMVm could boost host defense against antifungal-resistant C. glabrata under immunocompromised conditions
Methods: An immunocompromised mouse model was established using cyclophosphamide to mimic bloodstream infection with antifungal-resistant C. glabrata, and the therapeutic efficacy of WKYMVm was evaluated through survival, organ CFU, histology, and cytokine analyses. Emergency granulopoiesis was assessed by flow cytometry and qRT-PCR, autophagy by western blot and CYTO-ID staining, and neutrophil function and glycolytic activity by functional, metabolic, and molecular assays.
Results: WKYMVm administration improved survival in immunocompromised mice infected with C. glabrata, while reducing organ fungal burden and tissue damage. It increased neutrophil production and promoted autophagy-dependent maturation, yielding functionally active cells. Additionally, WKYMVm enhanced neutrophil immune functions through GLUT1-mediated metabolic activation, augmenting ROS production, degranulation, migration, and phagocytosis.
Conclusion: These findings indicate that FPR2 activation strengthens host defense against C. glabrata infection in immunocompromised mice by promoting neutrophil production, maturation, and functional activation. Overall, FPR2 activation represents a promising therapeutic approach for combating infections caused by antifungal-resistant fungi.
