IL-6 deficiency increases the susceptibility to tuberculosis infection of MHC-II congenic mouse strains
AbstractIntroduction. Excessive, poorly controlled inflammation in the lungs is one of the complications of the immune response during tuberculosis. On one hand, increased production of IL-6 in the lungs significantly correlates with the progression of tuberculosis in susceptible mice. On the other hand, a total deficiency of IL-6 on a tuberculosis-resistant genetic background leads to susceptibility to the infection. In this regard, the role of the cytokine IL-6 in the immune response during tuberculosis may differ between genetically sensitive and more resistant individuals.
Aim – to study the effect of IL-6 deficiency on the immune response and sensitivity to the infection in susceptible to tuberculosis MHC-II congenic mouse strains.
Material and methods. 2–3 months old females of IL-6-deficient B6.I.100.IL-6KO and B6.I.9.3.IL-6KO and wild-type B6.I.100 and B6.I.9.3 mice were used for aerosol infection with virulent strain M. tuberculosis H37Rv, 100 CFU/mouse. Determination of CFU numbers in the organs of infected animals was assessed by plating suspensions of lung and spleen cells on Dubos agar and macrocolonies counting after 21 days of cultivation. Cell surface phenotype and intracellular cytokine production after stimulation of lung cells with mycobacterial antigens in vitro were measured by flow cytometry. Lung cryosections were stained with hematoxylin and eosin.
Results. We found that IL-6 deficiency leads to a decreased lifespan after tuberculosis infection in the congenic strains B6.I.100.IL-6KO and B6.I.9.3.IL-6KO compared to the control animals B6.I.100 and B6.I.9.3, respectively. IL-6 deficiency also results in increased migration of neutrophils into the lungs of B6.I.9.3.IL-6KO mice at the beginning of the infection. Additionally, we observed lower numbers of specific IL-17-producing Th17 lymphocytes but a higher level of TNF-a production in the lungs of IL-6KO animals compared to wild-type controls. During the later stages of tuberculosis infection, we detected severe diffuse inflammation in the lungs of IL-6-deficient mice, whereas more concentrated areas of inflammation separated from uninfected lung tissue were observed in the lungs of wild-type animals.
Conclusion. IL-6 deficiency on the background of genetically determined high sensitivity to tuberculosis leads to an aggravation of the infection, which occurs due to mechanisms that differ from those realized in mice resistant to tuberculosis.
Keywords:tuberculosis; IL-6; IL-17; inflammation; lung pathology; susceptibility to infection
For citation: Linge I.A., Kapina M.A., Tsareva A.K., Kondratieva E.V., Apt A.S., Logunova N.N. IL-6 deficiency increases the susceptibility to tuberculosis infection of MHC-II congenic mouse strains. Immunologiya. 2024; 45 (2): 171–82. DOI: https://doi.org/10.33029/1816-2134-2024-45-2-171-182 (in Russian)
Funding. The study was supported by the grant of Russian Science Foundation No. 23-25-00087.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. Concept and design of the study – Linge I.A., Logunova N.N.; collection and processing of material – Linge I.A., Logunova N.N., Kapina M.A., Tsareva A.K., Kondratyeva E.V.; statistical processing – Linge I.A., Logunova N.N., Kapina M.A.; writing the text – Linge I.A., Apt A.S.; editing – Linge I.A., Logunova N.N., Apt A.S.
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