Activation of leukotriene B_(4)receptor 1 is a prerequisite for complement receptor 3-mediated antifungal responses of neutrophils  

作　　者：Yan Xin Sihan Xiong Linghong Zhou Xin Lin 

机构地区：[1]Institute for Immunology and School of Medicine,Tsinghua University,100084,Beijing,China [2]Tsinghua University-Peking University Center for Life Sciences,100084,Beijing,China [3]Department of Infectious Diseases,Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response,National Medical Center for Infectious Diseases,Huashan Hospital,Fudan University,Shanghai,200040,China

出　　处：《Cellular & Molecular Immunology》2024年第3期245-259,共15页中国免疫学杂志（英文版）

基　　金：supported by the National Key Research and Development Program of China(2019YFA0508502 to XL);National Natural Science Foundation of China(31930039,31821003,91942303 to XL);the General Financial Grant from the China Postdoctoral Science Foundation(2020M670301 to YX);annual funding from Tsinghua University-Peking University Jointed Center for Life Sciences.

摘　　要：Invasive fungal infections are life-threatening,and neutrophils are vital cells of the innate immune system that defend against them.The role of LTA4H-LTB_(4)-BLT1 axis in regulation of neutrophil responses to fungal infection remains poorly understood.Here,we demonstrated that the LTA4H-LTB_(4)-BLT1 axis protects the host against Candida albicans and Aspergillus fumigatus,but not Cryptococcus neoformans infection,by regulating the antifungal activity of neutrophils.Our results show that deleting Lta4h or Blt1 substantially impairs the fungal-specific phagocytic capacity of neutrophils.Moreover,defective activation of the spleen tyrosine kinase(Syk)and extracellular signal-related kinase(ERK1/2)pathways in neutrophils accompanies this impairment.Mechanistically,BLT1 regulates CR3-mediated,β-1,3-glucan-induced neutrophil phagocytosis,while a physical interaction with CR3 with slight influence on its dynamics is observed.Our findings thus demonstrate that the LTA4H-LTB_(4)-BLT1 axis is essential for the phagocytic function of neutrophils in host antifungal immune response against Candida albicans and Aspergillus fumigatus.

关 键 词：LTA4H BLT1 PHAGOCYTOSIS Complement receptor 3 FUNGI 

分 类 号：R392[医药卫生—免疫学]