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BCG and BCGΔBCG1419c transiently protects hyper-susceptible I/St mice and induce different influx of macrophages and neutrophils during pulmonary tuberculosisстатья
- Авторы: Korotetskaya Maria, Baikuzina Polina, Segura-Cerda Cristian Alfredo, de Jesús Aceves-Sánchez Michel, Apt Alexander, Flores-Valdez Mario Alberto
- Журнал: Journal of Medical Microbiology
- Том: 71
- Номер: 1
- Год издания: 2022
- Издательство: Society for General Microbiology
- Местоположение издательства: United Kingdom
- DOI: 10.1099/jmm.0.001485
- Аннотация: Host genetic factors influence both susceptibility to M. tuberculosis infection and immune responses generated by vaccination. Genetically TB-susceptible mice help to study mechanisms of immune protection which may differ from those operating in more resistant models. Methods: In this work, we compared the efficacy of protection conferred by subcutaneous vaccination of hypersusceptible I/St mice with BCG and the vaccine candidate BCGΔBCG1419c, against tuberculosis, measured as survival, weight loss, and replication in lungs. We further characterized the relative presence of immune cells in lungs. Results: We found that in I/St mice, vaccination with BCG or BCGΔBCG1419c provided similar level of protection against TB-driven weight loss and M. tuberculosis replication in lungs, while prolonging median survival time compared with unvaccinated controls. Despite affording similar protection to parental BCG, BCGΔBCG1419c led to a reduced presence of macrophages in lungs during early TB and to an increased neutrophil recruitment to the lungs during chronic TB. Conclusions: BCG ΔBCG1419c protects I/St mice in a different manner than wild type BCG against pulmonary tuberculosis by promoting different influx of macrophages and neutrophils at distinct stages of infection. These findings prompt us to suggest that preclinical evaluation of novel TB vaccine candidates should include evaluation of efficacy not only in commonly used resistant inbred mice but also in susceptible hosts to further determine their potential application to populations varying in their genetics, which would likely their resistance or susceptibility to tuberculosis.
- Добавил в систему: Коротецкая Мария Валерьевна