Authors:ZHUANG Li1,2,YANG Ling2,LI Linsheng2,YE Yuyang2,GONG Wenping1
Author Affilications:1Research Institute of Tuberculosis Medicine, Eighth Medical Center, PLA General Hospital; 2. Hebei North University
Corresponding authors: Gong Wenping, Email:[email protected]
Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention
Zhuang L, Yang L, Li L, Ye Z, Gong W.
MedComm (2020),2024 Jan 6; 5(1): and 419.
doi: 10.1002/mco2.419. eCollection 2024 Jan.
PMID: 38188605
1. Background
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (MTB) that seriously threatens human life and health. The history of MTB infection in humans can be traced back to the Stone Age, which is about 7,000 years ago. It was not until 1882 that the German bacteriologist Robert Koch (1843-1910) discovered and demonstrated that MTB was the causative agent of human tuberculosis. Subsequently, the combination of BCG and the invention of antibiotics led to significant advances in the prevention and treatment of tuberculosis. However, according to the World Health Organization's (WHO) Global Tuberculosis Report released in November 2023, TB remains the leading infectious disease causing human deaths, second only to COVID-19. Therefore, there are still many challenges in the prevention, diagnosis and treatment of tuberculosis, such as the lack of more effective vaccines, the inability to distinguish between latent tuberculosis infection and active tuberculosis, and the frequent occurrence of drug-resistant MTB.
Both our study and previous literature have found that tuberculosis is not only a contagious disease, but also an immune-related disease. Therefore, this review aims to analyze the interaction and mechanism between MTB and the host (including the host's immune response to MTB infection and the immune escape mechanism of MTB), tuberculosis diagnostic methods (including sputum examination, sputum culture, tuberculin skin test (TST), γ-interferon release assay (IGRA), etc.) and treatment options (multiple chemical drugs combined with chemotherapy) from the perspective of immunology), and explore the application value of biomarkers in the diagnosis and treatment of tuberculosis, as well as the chemotherapy and immunotherapy strategies for tuberculosis. We hope that through the perspective of immunology, we can provide new ideas and methods to address the challenges of TB prevention, diagnosis and treatment, and also provide potential possibilities for future development directions.
2. Immunological mechanisms of Mycobacterium tuberculosis-host interactions
Human understanding of tuberculosis has gone through three stages: anatomical stage, pathological stage and immune stage. A growing body of evidence suggests that TB is not only an infectious disease, but also an immune-mediated disease. This section will explore the mechanism of the host's immune response to MTB infection (Fig. 1) and the immune escape strategies adopted by MTB (Fig. 2) from the perspective of host-pathogen interactions.
Fig.1 Mechanism of immune response against Mycobacterium tuberculosis infection
Fig.2 Immune escape mechanism of Mycobacterium tuberculosis
3. Biomarkers for the diagnosis and treatment of tuberculosis
Currently, TB remains an important global infectious disease burden, especially in developing countries and very underdeveloped regions. Therefore, early diagnosis and treatment of TB is essential to reduce the morbidity and mortality of TB. However, currently available diagnostic techniques are insufficient to achieve an effective, rapid and accurate diagnosis of TB. Therefore, there is an urgent need for a simple, highly sensitive, and highly specific diagnostic method. This chapter focuses on the current application of multiple groups of biomarkers in the early diagnosis and treatment of tuberculosis, which provides a new direction and approach for finding new biomarkers and anti-tuberculosis drugs. However, research on these potential biomarkers is still in the preclinical research stage, and there is currently no universally applicable biomarker for the diagnosis and treatment of tuberculosis, and further clinical validation is needed. Still, these new exploratory studies offer hope for advancing the accuracy of TB diagnosis and the effectiveness of treatment. Table 1 lists the biomarkers for the diagnosis and treatment of tuberculosis that are currently in clinical research.
Table 1 Biomarkers for tuberculosis diagnosis and treatment that are currently in the research stage
4. Therapeutic intervention strategies for tuberculosis
Since the identification of MTB as a causative agent in 1882, significant progress has been made in its prevention, diagnosis, and treatment. In recent years, the incidence and mortality of tuberculosis have declined due to the development of anti-tuberculosis drugs and improvements in sanitation and living conditions. However, factors such as drug-resistant strains, immunosuppressants, drug addiction, poverty and population mobility have exacerbated the TB epidemic. When it comes to TB treatment strategies, effective prevention is the first priority. Currently, the only vaccine available for tuberculosis is BCG, but its effectiveness is limited, especially in adults. Second, to achieve a valid, rapid, and accurate TB diagnosis, there is currently a lack of effective methods to distinguish latent TB infection from active TB, which leads to delays and potential reactivation of TB treatment. Finally, it is crucial to employ effective treatments. The combination of multiple anti-tuberculosis drugs is the main method of treatment for tuberculosis. However, long-term use of multiple drugs can lead to toxicity, poor patient adherence, and the emergence of drug resistance. In addition, inappropriate antibiotic management and patient adherence issues have significantly increased the incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). All of these factors make TB prevention and control more challenging. Therefore, there is an urgent need to find new anti-TB drugs, improve the diagnostic capacity of TB, and develop new TB vaccines. With the rapid development of bioinformatics and immunology, new tuberculosis treatments have attracted much attention. Among them, the development of MTB-specific immunotherapy can effectively regulate the immune response against tuberculosis, providing a new avenue for comprehensive treatment and more effective prevention and intervention in high-risk groups.
V. Challenges and Prospects
Tuberculosis (TB) is a global infectious disease that seriously endangers human health and is the leading cause of death from a single infectious disease worldwide. The immune system plays a vital role in human defense against MTB invasion, a relationship that has been recognized for centuries. With the advancement of the global economy and scientific knowledge, immune-based anti-tuberculosis methods have attracted attention and made some progress. However, these methods also come with their own challenges. In the final part of this review, we will delve into the specific challenges and opportunities for TB prevention, diagnosis, and treatment (Figure 3).