2. Academic Validation
  3. Non-receptor tyrosine kinase c-Abl downstream of C-type lectin receptors regulates innate antifungal immunity through c-Cbl/MAPK pathway

Non-receptor tyrosine kinase c-Abl downstream of C-type lectin receptors regulates innate antifungal immunity through c-Cbl/MAPK pathway

  • Infect Immun. 2026 Mar 10;94(3):e0036525. doi: 10.1128/iai.00365-25.
Shu-Jun Ma # 1 2,  Ke-Fang Xie # 3 4,  Jie-Lin Duan # 5,  Xian-Long Wang 3,  Yi-Heng Yang 3,  Ying Wang 1
Affiliations

Affiliations

  • 1 Department of Dermatology, The First Affiliated Hospital of Naval Military Medical University, Shanghai, China.
  • 2 Department of Dermatology, The 926th Hospital of PLA, Kaiyuan, China.
  • 3 Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 4 School of Pharmacy, China Pharmaceutical University, Nanjing, China.
  • 5 Department of Respiratory and Critical Care Medicine, Institute of Respiratory Medicine, Dongguan Key Laboratory of Immune Inflammation and Metabolism, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.
  • # Contributed equally.
PMID: 41586506 DOI: 10.1128/iai.00365-25
Abstract

Non-receptor tyrosine kinase c-Abl is critical for host defense against Bacterial and viral infections, yet its role in Antifungal immunity remains elusive. Here, we report that inhibition of c-Abl with flumatinib mesylate significantly impairs the survival rate and exacerbates Fungal burden in mice infected with Candida albicans. Our findings reveal that c-Abl inhibition reduces production of TNF-α, IL-10, and IL-12 in bone marrow-derived dendritic cells (BMDCs) after stimulation with Fungal β-glucan or α-mannan. Mechanistically, c-Abl inhibition significantly blocks p38 and extracellular signal-regulated kinases 1/2 (ERK1/2) activation in BMDCs after α-mannan stimulation in a c-Cbl dependent manner. Collectively, our study uncovers a c-Abl/c-Cbl/MAPK signaling axis in dendritic cells that governs Antifungal innate immunity, highlighting c-Cbl as a critical downstream mediator linking c-Abl to host defense against C. albicans. Our findings provide a mechanistic basis for Fungal risk assessment in Cancer patients treated with c-Abl inhibitors.

Keywords

C. albicans; MAPKs; antifungal immunity; c-Abl; c-Cbl.

Figures
Products