THE COURSE OF TUBERCULOSIS INFECTION IN HYPER-SUSCEPTIBLE MICE CARRYING THE H2V HAPLOTYPE
- Authors: Baikuzina P.G.1,2, Gorbacheva DV.1,3, Apt A.S.1, KOROTETSKAYA M.V.1,3
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Affiliations:
- Central TВ Research Institute, Department of immunology, Laboratory of Immunogenetics, Moscow, Russia
- Skolkovo Institute of Science and Technology, Moscow, Russia
- Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16612
- DOI: https://doi.org/10.46235/1028-7221-16612-TCO
- ID: 16612
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Abstract
Abstract
Genetic regulation of the host susceptibility to Mycobacterium tuberculosis (Mtb) and severity of tuberculosis (TB) infection remain incompletely investigated. Identification of particular genes and involved in TB control and immune reactions regulated by these genes is essential for our understanding of pathogenesis of the disease, discovery of drug targets and rational vaccine development. We have shown that mice of the В10.SM (H2v) strain are extremely TB susceptible; meanwhile, the general genome structure of this mouse strain and the H2v haplotype itself are poorly characterized. We selected a pool of Mit genetic markers differentiating B10.SM mice from Chr. 17-congenic mice of the B10 strain by the PCR products motility in the electrophoresis setting. TB susceptibility of B10 mice is much lower than that of B10.SM. In the model of infection triggered by two different dosed of Mtb (100 and 600 CFU per mouse) administered via respiratory tract we demonstrated that B10.SM mice have significantly shorter survival time and significantly higher lung mycobacterial multiplication compared to B10 mice. We demonstrated (intracellular staining and ELISA) that IFN-γ production in the lungs of infected mice of the two strains corresponds well to their disease phenotypes. Thus, more resistant B10 mice possess significantly more lung IFN-γ-positive CD4+ T cells and a higher level of IFN-γ secretion.3
We have established (В10х В10.SM) F1 hybrids and demonstrated that the post-infection phenotypes of survival time, lung mycobacterial multiplication and IFN-γ production in these mice are intermediate compared to parental mice. Thus, we deal with the genetic trait with incomplete dominance expression. These data were confirmed in F2 hybrids by segregation genetic analysis. To characterize the phenotype of B10.SM mice in more detail, we vaccinated these mice with the BCG vaccine before TB challenge. Vaccination significantly prolonged survival time, diminished mycobacterial multiplication in the lungs and the degree of lung tissue pathology. Thus, a high level of susceptibility to primary infection did not interfere with BCG vaccination efficacy.
We intend to continue genetic and immunologic analyses of TB-hyper-susceptible B10.SM mice. Experimental data regarding the cause of extreme disturbances in protection against infection are prerequisite for our better understanding causality of the wide spectrum of TB manifestations in human populations, as well as for rational search for novel vaccines and medications against TB infection.
About the authors
Polina G. Baikuzina
Central TВ Research Institute, Department of immunology, Laboratory of Immunogenetics, Moscow, Russia;Skolkovo Institute of Science and Technology, Moscow, Russia
Email: polinabaikuzina@gmail.com
ORCID iD: 0000-0001-5005-7214
SPIN-code: 6121-2259
Scopus Author ID: 57430699500
Research Assistant, Laboratory for Immunogenetics, Department of Immunology, Central TВ Research Institute; Technician, Skolkovo Institute of Science and Technology
Russian Federation, 107564, Moscow, Yauza alley, 2D V. Gorbacheva
Central TВ Research Institute, Department of immunology, Laboratory of Immunogenetics, Moscow, Russia;Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia
Email: galvaniccell@gmail.com
Research Assistant, Laboratory for Immunogenetics, Department of Immunology, Central TВ Research Institute; Undergraduate Student, Faculty of Bioengineering and Bioinformatics, M. V. Lomonosov Moscow State University
Russian Federation, 107564, Moscow, Yauza alley, 2
Alex S. Apt
Central TВ Research Institute, Department of immunology, Laboratory of Immunogenetics, Moscow, Russia
Email: alexapt0151@gmail.com
Scopus Author ID: 7006958166
PhD, Professor and Head, Laboratory for Immunogenetics, Department of Immunology, Central TВ Research Institute
Russian Federation, 107564, Moscow, Yauza alley, 2
Mariya V. KOROTETSKAYA
Central TВ Research Institute, Department of immunology, Laboratory of Immunogenetics, Moscow, Russia;Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia
Author for correspondence.
Email: mkorotetskaya@gmail.com
ORCID iD: 0000-0002-5885-1129
Scopus Author ID: 25958092400
Senior Staff Scientist, Laboratory for Immunogenetics, Department of immunology, Central TВ Research Institute
Russian Federation, 107564, Moscow, Yauza alley, 2References
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