Bid-Induced Release of AIF/EndoG from Mitochondria Causes Apoptosis of Macrophages during Infection with Leptospira interrogans
Authors: Hai-Yan Dong
Yang Li
Shi-Jun Li
Jie Yan
Wei-Lin Hu
David M Ojcius
Journal: Frontiers in Cellular and Infection Microbiology (2017)
Discipline: MICROBIOLOGY
Keywords: AIF; Bid; EndoG; Leptospira; apoptosis
Affiliations: Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, 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, Hangzhou, China., Department of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, China., Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, CA, United States., Institute of Communicable Disease Control and Prevention, Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Concern about Figure 1E. * Red boxes: part of the top 1h panel appears to look similar to the top 2h panel. ![file] , 
 Dear Elisabeth, Dear Elisabeth, I am writting to you on behalf of professor Jie Yan (the corresponding author) , because his account and email address (med_bp@zju.edu.cn) seems not working in Pubpeer. He has tried to write response comment using his account, but we can not see the details of the response comment in Peerbub. He also contact the curator of Peerpub for help. The following response is from Jie yan:  Thank you for your comment. We are checking the data and will response soon. All the best, Shijun , 
 Dear Dr. Li, Thank you for letting me know. I look forward to you or Dr. Yan s reply. , 
 #1 Thank you for your comment. Although this paper was published in 2017, this part of the figure was based on experiments done in 2008 by the second author. We no longer have the original data and are repeating the experiment. We will contact the journal for advice on what to do. ,