Overexpression of LAG-3: a potential indicator of low immune function in tuberculosis

• Published in: Frontiers in cellular and infection microbiology Vol. 14; p. 1410015
• Main Authors: Pan, Yun, Yao, Zengxi, Huang, Lifen, Xu, Meina, Chen, Ruichang, Li, Dengsheng, Wang, Xinyuan, Wu, Jianchao, Li, Minran, Liang, Xujing, Tan, Jiaxiong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18-06-2024
• Subjects: Animals; Antigens, CD - genetics; BCG Vaccine - immunology; CD8+ T cell; CD8-Positive T-Lymphocytes - immunology; Cellular and Infection Microbiology; Gene Expression Profiling; Humans; immune checkpoint; Interleukin-12 - genetics; Interleukin-12 - metabolism; Interleukin-2 - genetics; Interleukin-2 - metabolism; lymphocyte activation gene 3; Lymphocyte Activation Gene 3 Protein; Macrophages - immunology; Macrophages - microbiology; Male; mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - immunology; Perforin - genetics; Perforin - metabolism; tuberculosis; Tuberculosis - immunology; Tuberculosis - microbiology; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; mycobacterium tuberculosis; lymphocyte activation gene 3; CD8+ T cell; immune checkpoint; tuberculosis
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2024.1410015

Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB.
We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed.
The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination.
LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.