Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis
Authors: Xu Chen
Ai-Hua Sun
Jie Yan
Xu&#x27;ai Lin
Shi-Jun Li
Wei-Lin Hu
David M Ojcius
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: leptospirosis; phagocytes; macrophages; neutrophils; killing mechanism
Affiliations: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, P.R. China., Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. 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, Zhejiang, P.R. China., Guizhou Provincial Center for Disease Control and Prevention, Guiyang, Guizhou, P.R. China., Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, California, United States of America., Faculty of Basic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, P.R. China.

Abstract:  Objective: To identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans. Methods: Major infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry. Results: Peripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver and kidneys of infected mice. Levels of macrophage- but not neutrophil-specific chemokines and VECAMs were significantly increased in the samples from infected mice and patients. All macrophages tested had a higher ability than neutrophils to phagocytose and kill leptospires. Higher ROS and NO levels and [Ca2+]i in the macrophages were involved in killing leptospires. Human macrophages displayed more phagolysosome formation and a stronger leptospire-killing ability to than mouse macrophages. Conclusions: Mononuclear-macrophages but not neutrophils represent the main infiltrating and anti-leptospiral phagocytes during leptospirosis. A lower level of phagosome-lysosome fusion may be responsible for the lower Leptospira-killing ability of human macrophages. 

Retracted: No

PubPeer comments:
 Figure 6A. * Red boxes: The left and right  Normal Lung panels appear to show an overlap if one of them is rotated 90 degrees. ![file] , 
 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 analysis. 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 Dear Bik, Thank you for your analysis. We are checking the data and will repeat the experiment if need be. ,