Abstract
It is widely accepted that different strains of Mycobacterium tuberculosis have variable degrees of pathogenicity and induce different immune responses in infected hosts. Similarly, different strains of Mycobacterium bovis have been identified but there is a lack of information regarding the degree of pathogenicity of these strains and their ability to provoke host immune responses. Therefore, in the current study, we used a mouse model to evaluate various factors involved in the severity of disease progression and the induction of immune responses by two strains of M. bovis isolated from cattle. Mice were infected with both strains of M. bovis at different colony-forming unit (CFU) via inhalation. Gross and histological findings revealed more severe lesions in the lung and spleen of mice infected with M. bovis N strain than those infected with M. bovis C68004 strain. In addition, high levels of interferon-γ (IFN-γ), interleukin-17 (IL-17), and IL-22 production were observed in the serum samples of mice infected with M. bovis N strain. Comparative genomic analysis showed the existence of 750 single nucleotide polymorphisms and 145 small insertions/deletions between the two strains. After matching with the Virulence Factors Database, mutations were found in 29 genes, which relate to 17 virulence factors. Moreover, we found an increased number of virulent factors in M. bovis N strain as compared to M. bovis C68004 strain. Taken together, our data reveal that variation in the level of pathogenicity is due to the mutation in the virulence factors of M. bovis N strain. Therefore, a better understanding of the mechanisms of mutation in the virulence factors will ultimately contribute to the development of new strategies for the control of M. bovis infection.
Highlights
Tuberculosis (TB) remains one of the most important infectious diseases of humans and animals worldwide
We analyzed the genetic differences of two M. bovis strains in mouse models that were isolated from cattle with different backgrounds
BALB/c and C57Bl/6 mice are the most classical tuberculosis resistant animal models and are widely used for M. tuberculosis or M. bovis studies, both of them show limited features of tuberculosis pathophysiology when compared with the C3HeB/FeJ mouse model [24,37,38]
Summary
Tuberculosis (TB) remains one of the most important infectious diseases of humans and animals worldwide. Like many other developing countries, control of bovine tuberculosis remains a challenge in China, which is mainly caused by M. bovis. Tuberculosis consists of multiple stages that depend on both the pathogen and the host immune response to the infection [3,4]. Innate immune responses play an important role in bacterial control. There is increasing evidence that genetic variation among mycobacterial isolates contributes to differences in immune response induction and disease progression [5,6,7,8]. Variability in the innate immune responses to genetic differences among M. bovis strains remains poorly understood. A better understanding of the genetic factors involved in immune response to infection will contribute to the control of bovine tuberculosis
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