Molecular markers of M. tuberculosis virulence in lung tissue (experimental study)

Abstract

To use a biological model, in order to determine significant molecular immunohistochemical markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of the M. tuberculosis Beijing genotype in lung tissue. Lung samples of the C57BL/6 male mice were obtained during experimental infection with M. tuberculosis strains: the reference laboratory strain H37Rv, multidrug-resistant clinical strains 396 (highly lethal and hypervirulent «Buryat» genotype Beijing 14717-15) and 6691 (low-lethal and low-virulent "Omsk" genotype Beijing 1071-32) on days 14, 21, 60 and 120. They were studied by histological and immunohistochemical methods. The relative areas of expression of IL-6, IL-12A, iNOS, and TNF-α in the lung tissue of model animals were established. A study of strain 396 showed that both disease progression and damage to lung tissue are associated with a highly reactive immune response and increased synthesis of iNOS and strain characteristics that block the production of TNF-α. On the contrary, for strain 6691 a low reactivity of the immune response was revealed, with statistically significantly lower values of the relative area of expression of NOS and TNF-α during all observation periods (days 14-120). All animals that survived to day 120 showed a similar morphological picture with differences in cytokine levels, indicating a nonlinear relationship between proinflammatory factors and the damage substratum. The progression of the disease and damage of lung tissue were associated with a highly reactive immune response and increased synthesis of iNOS, strain properties that block the TNF-α production. Thus, iNOS and TNF-α can act as molecular markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of M. tuberculosis in lung tissue.