Abstract
Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.
Highlights
Mycobacterium tuberculosis is an infectious agent that causes asymptomatic latent, chronic infection and can provoke active disease in man and animals
Our study indicates that Bacillus Calmette-Guerin (BCG)-mycobacteria in granuloma cells obtained from various organs of mice with chronic TB infection are functionally heterogeneous
Because none of the mice had been observed to have acute tuberculous infection at the time of granuloma isolation, it was concluded that these granulomas were isolated at the latent, chronic stage of BCG infection
Summary
Mycobacterium tuberculosis is an infectious agent that causes asymptomatic latent, chronic infection and can provoke active disease in man and animals. Studies of the mechanisms of mycobacterial survival in the host organisms during latent TB infection and the mechanisms of their reactivation and replication are extremely important for the development of new vaccines, medicines, and methods for tuberculosis treatment. The bacteriological method, which is generally used for assessing the multiplicity of mycobacterial infection in animal organs and tissues, involves inoculation of their homogenates on special agar media and counting colony-forming units This allows only generalized data on the number of mycobacteria during latent infection to be obtained [12,13,14,15,16]. Neither inspecting mycobacteria on the histological sections of animal tissues [17,18,19,20] nor in vivo studies of granulomas [21] in the livers of mice infected with BCG, an attenuated live strain of Mycobacterium bovis, allow the multiplicity of infection (MOI) in the granuloma cells to be inferred
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