Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection

Fanlei Ran; Yaguo Wang; Guoqin Zhang; Haiyan Guo; Jinlong Li; Xilin Zhang; Zhilong Wu; Lijun Bi

doi:10.1016/j.micpath.2024.106681

Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection

Microb Pathog. 2024 May 15:192:106681. doi: 10.1016/j.micpath.2024.106681. Online ahead of print.

Authors

Fanlei Ran¹, Yaguo Wang², Guoqin Zhang³, Haiyan Guo⁴, Jinlong Li⁵, Xilin Zhang⁶, Zhilong Wu⁷, Lijun Bi⁸

Affiliations

¹ Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Guangzhou National Laboratory, Guangzhou, 510005, China.
² Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; TB Healthcare Co., Ltd., Foshan, 528300, China.
³ Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
⁴ Department of Geriatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, 518107, China.
⁵ TB Healthcare Co., Ltd., Foshan, 528300, China.
⁶ Foshan Fourth People's Hospital, Foshan, 528000, China. Electronic address: zhangxlsn@163.com.
⁷ Foshan Fourth People's Hospital, Foshan, 528000, China. Electronic address: wuzlfs@163.com.
⁸ Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Guangzhou National Laboratory, Guangzhou, 510005, China. Electronic address: blj@ibp.ac.cn.

PMID: 38754565
DOI: 10.1016/j.micpath.2024.106681

Abstract

Tuberculosis (TB) is a major fatal infectious disease globally, exhibiting high morbidity rates and impacting public health and other socio-economic factors. However, some individuals are resistant to TB infection and are referred to as "Resisters". Resisters remain uninfected even after exposure to high load of Mycobacterium tuberculosis (Mtb). To delineate this further, this study aimed to investigate the factors and mechanisms influencing the Mtb resistance phenotype. We assayed the phagocytic capacity of peripheral blood mononuclear cells (PBMCs) collected from Resisters, patients with latent TB infection (LTBI), and patients with active TB (ATB), following infection with fluorescent Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Phagocytosis was stronger in PBMCs from ATB patients, and comparable in LTBI patients and Resisters. Subsequently, phagocytes were isolated and subjected to whole transcriptome sequencing and small RNA sequencing to analyze transcriptional expression profiles and identify potential targets associated with the resistance phenotype. The results revealed that a total of 277 mRNAs, 589 long non-coding RNAs, 523 circular RNAs, and 35 microRNAs were differentially expressed in Resisters and LTBI patients. Further, the endogenous competitive RNA (ceRNA) network was constructed from differentially expressed genes after screening. Bioinformatics, statistical analysis, and quantitative real-time polymerase chain reaction were used for the identification and validation of potential crucial targets in the ceRNA network. As a result, we obtained a ceRNA network that contributes to the resistance phenotype. TCONS_00034796-F3, ENST00000629441-DDX43, hsa-ATAD3A_0003-CYP17A1, and XR_932996.2-CERS1 may be crucial association pairs for resistance to TB infection. Overall, this study demonstrated that the phagocytic capacity of PBMCs was not a determinant of the resistance phenotype and that some non-coding RNAs could be involved in the natural resistance to TB infection through a ceRNA mechanism.

Keywords: LTBI; Phagocytes; Resisters; Tuberculosis; ceRNA.