Bid-Induced Release of AIF/EndoG from Mitochondria Causes Apoptosis of Macrophages during Infection with Leptospira interrogans

Frontiers in Cellular and Infection Microbiology

Yan, Jie¹  Li, Yang²  Ojcius, David M.³  Hu, Wei-Lin³  Dong, Hai-Yan⁴  Li, Shi-Jun⁴ 

[1] Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, United States;Department of Medical Microbiology and Immunology, Wenzhou Medical University, China;Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, China;Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, China

关键词: Apoptosis;    Leptospira;    BID;    AIF;    EndoG;    macrophage;   

DOI  :  10.3389/fcimb.2017.00471

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although the release of mitochondrial apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was not activated. Next, we found that the release and translocation of AIF and/or EndoG was preceded by the activation of the BH3-interacting domain death agonist (Bid). Furthermore, our data demonstrated that caspase-8 was activated during the infection and caused the activation of Bid. Meanwhile, high reactive oxygen species (ROS) trigged by the infection caused the dephosphorylation of Akt, which also activated Bid. In conclusion, Bid-mediated mitochondrial release of AIF and/or EndoG followed by nuclear translocation is a major mechanism of leptospire- induced apoptosis in macrophages, and this process is modulated by both caspase-8 and ROS-Akt signal pathways.

【 授权许可】

CC BY