Activation of leukotriene B 4 receptor 1 is a prerequisite for complement receptor 3-mediated antifungal responses of neutrophils.

Autor: Xin Y; Institute for Immunology and School of Medicine, Tsinghua University, 100084, Beijing, China.; Tsinghua University-Peking University Center for Life Sciences, 100084, Beijing, China., Xiong S; Institute for Immunology and School of Medicine, Tsinghua University, 100084, Beijing, China., Zhou L; 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., Lin X; Institute for Immunology and School of Medicine, Tsinghua University, 100084, Beijing, China. linxin307@tsinghua.edu.cn.; Tsinghua University-Peking University Center for Life Sciences, 100084, Beijing, China. linxin307@tsinghua.edu.cn.
Jazyk: angličtina
Zdroj: Cellular & molecular immunology [Cell Mol Immunol] 2024 Mar; Vol. 21 (3), pp. 245-259. Date of Electronic Publication: 2024 Jan 31.
DOI: 10.1038/s41423-024-01130-4
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to CSI and USTC.)
Databáze: MEDLINE
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