Comparative transcriptomics reveals common and strain-specific responses of human macrophages to infection with Mycobacterium tuberculosis and Mycobacterium bovis BCG

Li, Pei1,2; Li, Yang1; Wang, Cun Chuan1; Xia, Li Gang1

2024-04-01

10.1016/j.micpath.2024.106593

MICROBIAL PATHOGENESIS   影响因子和分区

0882-4010

1096-1208

Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (M. bovis) are closely related pathogenic mycobacteria known to cause chronic pulmonary infections in both humans and animals. Despite sharing nearly identical genomes and virulence factors, these two bacteria display variations in host tropism, epidemiology, and clinical presentations. M. bovis Bacillus Calmette-Gue ' rin (BCG) is an attenuated strain of M. bovis commonly utilized as a vaccine for tuberculosis (TB). Nevertheless, the molecular underpinnings of these distinctions and the intricacies of host-pathogen interactions remain areas of ongoing research. In this study, a comparative transcriptomic analysis was conducted on human leukemia macrophages (THP-1) infected with either MTB H37Rv or M. bovis BCG (Tokyo strain) to elucidate common and strain-specific responses at the transcriptional level. RNA sequencing was utilized to characterize the transcriptomes of human primary macrophages infected with MTB or BCG at 6 and 24 h post-infection. The findings indicate that both MTB and BCG induce substantial and dynamic alterations in the transcriptomes of THP-1, with a notable overlap in the quantity and extent of differentially expressed genes (DEGs). Moreover, gene ontology (GO) enrichment analysis unveiled shared pathways related to immune response, cytokine signaling, and apoptosis. The immune response of macrophages to bacterial infections at 6 h exhibited significantly greater intensity compared to that at 24 h. Furthermore, distinct gene sets displaying notable variances between MTB and BCG infections were identified. The profound impact of MTB infection on macrophage gene expression, particularly within the initial 6 h, was evident. Additionally, downregulation of pathways such as Focal adhesion, Rap1 signaling pathway, and Regulation of actin cytoskeleton was observed. The pathways associated with inflammation reactions and cell apoptosis exhibited significant differences, with BCG triggering macrophage apoptosis and MTB enhancing the survival of intracellular bacteria. Our findings reveal that MTB and BCG provoke similar yet distinct transcriptional responses in human macrophages, indicating variations in their pathogenesis and ability to adapt to host environments. These results offer novel insights into the molecular mechanisms governing host-pathogen interactions and may contribute to a deeper understanding of TB pathogenesis.

Macrophages Transcriptomics Mycobacterium tuberculosis Bacillus Calmette -Gue ' rin Apoptosis

SCI

英语

第一 ; 通讯

Immunology ; Microbiology

Immunology ; Microbiology

WOS:001206392500001

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

IMMUNOLOGY

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp,Div Gastrointestinal Surg, Affiliated Hosp 1,Clin Med Coll 2,Dept Gen Surg, Shenzhen 518020, Guangdong, Peoples R China
2.Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Systemat Immunol TB, Shenzhen, Peoples R China

Li, Pei,Li, Yang,Wang, Cun Chuan,et al. Comparative transcriptomics reveals common and strain-specific responses of human macrophages to infection with Mycobacterium tuberculosis and Mycobacterium bovis BCG[J]. MICROBIAL PATHOGENESIS,2024,189.

Li, Pei,Li, Yang,Wang, Cun Chuan,&Xia, Li Gang.(2024).Comparative transcriptomics reveals common and strain-specific responses of human macrophages to infection with Mycobacterium tuberculosis and Mycobacterium bovis BCG.MICROBIAL PATHOGENESIS,189.

Li, Pei,et al."Comparative transcriptomics reveals common and strain-specific responses of human macrophages to infection with Mycobacterium tuberculosis and Mycobacterium bovis BCG".MICROBIAL PATHOGENESIS 189(2024).