2. Academic Validation
  3. EPHA5 regulates antifungal innate immunity by phosphorylating EPHB2 and Dectin-1

EPHA5 regulates antifungal innate immunity by phosphorylating EPHB2 and Dectin-1

  • PLoS Pathog. 2025 Jun 9;21(6):e1013179. doi: 10.1371/journal.ppat.1013179.
Ru Gao 1,  Heping Wang 1,  Zhihui Cui 1,  Yanyun Du 2 3 4 5 6,  Ruirui He 2 3 4 5 6,  Lingyun Feng 2 3 4 5,  Bo Zeng 2 3 4 5,  Yangyang Li 2 3 4 5,  Guoling Huang 5,  Ting Pan 5,  Yuan Wang 5,  Ming Yi 2 3 4 5,  Chenhui Wang 2 3 4 5 6
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • 2 The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
  • 3 Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
  • 4 Sichuan Medical Laboratory Clinical Medical Research Center, Sichuan Provincial People's Hospital, Chengdu, China.
  • 5 School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • 6 Key Laboratory of Personalized Medicine Research and Treatment of Sichuan Province, Sichuan Provincial People's Hospital, Chengdu, China.
PMID: 40489568 DOI: 10.1371/journal.ppat.1013179
Abstract

Invasive Fungal infections (IFIs) have emerged as a significant health threat and cause approximately 3.75 million deaths per year globally. Understanding the detailed mechanism of the immune response to eliminate invasive Fungal pathogens may help to provide new insights for the development of Antifungal methods and drugs. Previously, we reported that the tyrosine kinase receptor EPH receptor B2 (EphB2) is a coreceptor of β-glucan and phosphorylates Syk to activate the Antifungal downstream signaling pathway. However, how EphB2 is activated after fungal Infection is still unknown. In this study, we show that EphA5 plays a critical role in Antifungal immunity by phosphorylating EphB2 and Dectin-1 after fungal Infection, which facilitates the recruitment and activation of Syk and subsequent activation of downstream Antifungal signaling pathways. Additionally, we showed that EphA5-deficient mice exhibited increased susceptibility to Candida albicans Infection, with increased Fungal burdens and impaired immune cell recruitment. This study provides not only a mechanistic explanation for EphB2 and Dectin-1 activation after fungal Infection but also new insights into potential therapeutic strategies for treating IFIs.

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