Comprehensive analyses of transcriptomes induced by Lyme spirochete infection to CNS model system

Shiyuan Wen; Xin Xu; Jing Kong; Lisha Luo; Peng Yue; Wenjing Cao; Yu Zhang; Meixiao Liu; Yuxin Fan; Jingjing Chen; Mingbiao Ma; Lvyan Tao; Yun Peng; Feng Wang; Yan Dong; Bingxue Li; Suyi Luo; Guozhong Zhou; Taigui Chen; Lianbao Li; Aihua Liu; Fukai Bao

doi:10.1016/j.meegid.2022.105349

Comprehensive analyses of transcriptomes induced by Lyme spirochete infection to CNS model system

Infect Genet Evol. 2022 Sep:103:105349. doi: 10.1016/j.meegid.2022.105349. Epub 2022 Aug 12.

Authors

Shiyuan Wen¹, Xin Xu², Jing Kong³, Lisha Luo³, Peng Yue³, Wenjing Cao³, Yu Zhang², Meixiao Liu², Yuxin Fan², Jingjing Chen³, Mingbiao Ma⁴, Lvyan Tao⁵, Yun Peng², Feng Wang², Yan Dong², Bingxue Li³, Suyi Luo², Guozhong Zhou², Taigui Chen², Lianbao Li², Aihua Liu⁶, Fukai Bao⁷

Affiliations

¹ Department of Microbiology and Immunology, Kunming Medical University, Kunming 650500, China; Department of Intensive Care Unit, First People's Hospital of Yunnan Province, Kunming 650500, China.
² Department of Microbiology and Immunology, Kunming Medical University, Kunming 650500, China.
³ Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China.
⁴ Department of Microbiology and Immunology, Kunming Medical University, Kunming 650500, China; Yunnan Province Key Laboratory of Children's Major Diseases Research, The Affiliated Children's Hospital of Kunming, Kunming Medical University, Kunming 650030, China.
⁵ Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China; Yunnan Province Key Laboratory of Children's Major Diseases Research, The Affiliated Children's Hospital of Kunming, Kunming Medical University, Kunming 650030, China.
⁶ Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming 650500, China; Yunnan Province Key Laboratory of Children's Major Diseases Research, The Affiliated Children's Hospital of Kunming, Kunming Medical University, Kunming 650030, China; The Institute for Tropical Medicine, Kunming Medical University, Kunming 650500, China; Yunnan Demonstration Base of International Science and Technology Cooperation for Tropical Diseases, Kunming 650500, China. Electronic address: liuaihua@kmmu.edu.cn.
⁷ Department of Microbiology and Immunology, Kunming Medical University, Kunming 650500, China; Yunnan Province Key Laboratory of Children's Major Diseases Research, The Affiliated Children's Hospital of Kunming, Kunming Medical University, Kunming 650030, China; The Institute for Tropical Medicine, Kunming Medical University, Kunming 650500, China; Yunnan Demonstration Base of International Science and Technology Cooperation for Tropical Diseases, Kunming 650500, China. Electronic address: baofukai@kmmu.edu.cn.

PMID: 35964914
DOI: 10.1016/j.meegid.2022.105349

Abstract

Background: Lyme disease is a zoonotic disease caused by infection with Borrelia burgdorferi (Bb), the involvement of the nervous system in Lyme disease is usually referred to as Lyme neuroborreliosis (LNB). LNB has diverse clinical manifestations, most commonly including meningitis, Bell's palsy, and encephalitis. However, the molecular pathogenesis of neuroborreliosis is still poorly understood. Comprehensive transcriptomic analysis following Bb infection could provide new insights into the pathogenesis of LNB and may identify novel biomarkers or therapeutic targets for LNB diagnosis and treatment.

Methods: In the present study, we pooled transcriptomic dataset of Macaca mulatta (rhesus) from our laboratory and the human astrocyte dataset GSE85143 from the Gene Expression Omnibus database to screen common differentially expressed genes (DEGs) in the Bb infection group and the control group. Functional and enrichment analyses were applied for the DEGs. Protein-Protein Interaction network, and hub genes were identified using the Search Tool for the Retrieval of Interaction Genes database and the CytoHubba plugin. Finally, mRNA expression of hub genes was validated in vitro and ex vivo from Bb infected models and normal controls by quantitative reverse transcription PCR (qRT-PCR).

Results: A total of 80 upregulated DEGs and 32 downregulated DEGs were identified. Among them, 11 hub genes were selected. The pathway enrichment analyses on 11 hub genes revealed that the PI3K-Akt signaling pathway was significantly enriched. The mRNA levels of ANGPT1, TLR6, SREBF1, LDLR, TNC, and ITGA2 in U251 cells and/or rhesus brain explants by exposure to Bb were validated by qRT-PCR.

Conclusion: Our study suggested that TLR6, ANGPT1, LDLR, SREBF1, TNC, and ITGA may be candidate mammal biomarkers for LNB, and the TLR6/PI3K-Akt signaling pathway may play an important role in LNB pathogenesis.

Keywords: Borrelia burgdorferi; Candidate biomarkers; Lyme neuroborreliosis; Pathogenesis; Transcriptomic analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Borrelia burgdorferi Group* / genetics
Borrelia burgdorferi* / genetics
Central Nervous System
Humans
Lyme Neuroborreliosis*
Macaca mulatta / genetics
Mammals
Phosphatidylinositol 3-Kinases / genetics
Proto-Oncogene Proteins c-akt / genetics
RNA, Messenger
Toll-Like Receptor 6 / genetics
Transcriptome

Substances

Biomarkers
RNA, Messenger
Toll-Like Receptor 6
Proto-Oncogene Proteins c-akt