The immunological mechanism and cause of tuberculosis worsening and progressing to severe tuberculosis when infected with the virus after infection with Mycobacterium tuberculosis have been revealed by domestic medical researchers. This study is expected to provide a basis for and understanding of the treatment of tuberculosis patients and the development of the next-generation tuberculosis vaccine.
Professor Shin Sung-jae and Kwon Ki-woong of the Department of Microbiology at Yonsei University College of Medicine, and a research team led by Professor Sang-Jun Ha, In-Seok Lee, and Dr. Tae-Gun Kang of Yonsei University College of Life Systems revealed the immunological mechanism and key factors that progress from tuberculosis infection to viral infection through a mouse model on the 13th. Through this, a method and principle to effectively control tuberculosis exacerbation were presented. The results of this study were published in the latest issue of the international academic journal ‘Nature Communications (IF 14.919)’.
Tuberculosis is the most serious infectious disease among the three major infectious diseases designated by the World Health Organization (WHO) along with AIDS and malaria. It is estimated that approximately 2 billion people worldwide are currently infected with Mycobacterium tuberculosis. According to the Korea Centers for Disease Control and Prevention (KCDC), although the prevalence of tuberculosis in Korea is dropping significantly compared to the past, the incidence and mortality rates of tuberculosis in 2021 are still among the highest among OECD member countries.
Among tuberculosis patients, active tuberculosis patients may progress to severe tuberculosis accompanied by severe lung pathology. Recently, the importance of tuberculosis management is increasing due to the increase of multidrug-resistant Mycobacterium tuberculosis, the increase of highly pathogenic Mycobacterium tuberculosis, and the spread of the COVID-19 virus.
After establishing a mouse model infected with Mycobacterium tuberculosis, the research team compared the progression of tuberculosis between the two groups by co-infecting some mice with the lymphocytic meningitis virus, which induces an immune response.
As a result, no serious lung pathology was observed in the Mycobacterium tuberculosis mono-infected group, but extensive lung inflammation with necrotizing granuloma was observed in the virus co-infected group, and a very high level of Mycobacterium tuberculosis proliferation was observed.
The research team confirmed the exacerbation of tuberculosis pathology caused by viral infection and the mechanism of excessive Mycobacterium tuberculosis proliferation by analyzing the immune response to the lung tissue and draining lymph nodes of the mouse model.
As a result of the immune response analysis, it was found that, after exposure to Mycobacterium tuberculosis, type 1 interferon was excessively increased due to viral infection, and as a result, Mycobacterium tuberculosis-specific T cells essential for the control of Mycobacterium tuberculosis decreased in the lung tissue.
In addition, the research team classified the Mycobacterium tuberculosis mono-infected group, the virus co-infected bacteria, and the virus-co-infected bacteria into three groups treated with a type 1 interferon receptor neutralizing antibody, and conducted a single-cell-level precise transcriptome analysis of immune cells in the lung tissue.
As a result, the neutralizing antibody-treated group did not show severe tuberculosis accompanied by aggravated lung pathology due to virus co-infection, the same as the Mycobacterium tuberculosis single infection group.
It was confirmed that type 1 interferon suppressed the expression of chemokines CXCL9 and CXCL10 produced by specific macrophages in lung tissue. The chemokine is known to be a factor that promotes the influx of activated T cells from the lymph node to the infected tissue. The decrease in chemokines leads to a decrease in the influx of activated Mycobacterium tuberculosis-specific T cells into the lung tissue, and also decreases the Mycobacterium tuberculosis-specific T-cell-derived type 2 interferon, which fails to control the active proliferation of Mycobacterium tuberculosis and induces pulmonary immunopathology.
Professor Shin Sung-jae said, “Through this study, we were able to elucidate the mechanism of severe tuberculosis caused by viral infection. We look forward to contributing to the development.”
Meanwhile, this research was carried out with the support of the National Research Foundation’s mid-level researcher support project, the leading research center project, and the vaccine commercialization technology development project of the Health Industry Promotion Agency.