An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host
The role of neutrophils in tuberculosis infection remains less well studied compared to that of the CD4<sup>+</sup> T-lymphocytes and macrophages. Thus, alterations in <i>Mycobacterium tuberculosis</i> transcription profile following phagocytosis by neutrophils and how these...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/2961 |
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| author | Elena Kondratieva Konstantin Majorov Artem Grigorov Yulia Skvortsova Tatiana Kondratieva Elvira Rubakova Irina Linge Tatyana Azhikina Alexander Apt |
| author_facet | Elena Kondratieva Konstantin Majorov Artem Grigorov Yulia Skvortsova Tatiana Kondratieva Elvira Rubakova Irina Linge Tatyana Azhikina Alexander Apt |
| author_sort | Elena Kondratieva |
| collection | DOAJ |
| description | The role of neutrophils in tuberculosis infection remains less well studied compared to that of the CD4<sup>+</sup> T-lymphocytes and macrophages. Thus, alterations in <i>Mycobacterium tuberculosis</i> transcription profile following phagocytosis by neutrophils and how these shifts differ from those caused by macrophage phagocytosis remain unknown. We developed a mouse model that allows obtaining large amounts of either neutrophils or macrophages infected in vivo with <i>M. tuberculosis</i> for mycobacteria isolation in quantities sufficient for the whole genome RNA sequencing and aerosol challenge of mice. Here, we present: (i) the differences in transcription profiles of mycobacteria isolated from liquid cultures, neutrophils and macrophages infected in vivo; (ii) phenotypes of infection and lung inflammation (life span, colony forming units (CFU) counts in organs, lung pathology, immune cells infiltration and cytokine production) in genetically TB-susceptible mice identically infected via respiratory tract with neutrophil-passaged (NP), macrophage-passaged (MP) and conventionally prepared (CP) mycobacteria. Two-hour residence within neutrophils caused transcriptome shifts consistent with mycobacterial transition to dormancy and diminished their capacity to attract immune cells to infected lung tissue. Mycobacterial multiplication in organs did not depend upon pre-phagocytosis, whilst survival time of infected mice was shorter in the group infected with NP bacilli. We also discuss possible reasons for these phenotypic divergences. |
| first_indexed | 2024-03-09T19:43:29Z |
| format | Article |
| id | doaj.art-8b663fe50109422888d6a67c1abab5e1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:43:29Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8b663fe50109422888d6a67c1abab5e12023-11-24T01:29:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236296110.3390/ijms23062961An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse HostElena Kondratieva0Konstantin Majorov1Artem Grigorov2Yulia Skvortsova3Tatiana Kondratieva4Elvira Rubakova5Irina Linge6Tatyana Azhikina7Alexander Apt8Laboratory for Immunogenetics, Central Research TB Institute, 107564 Moscow, RussiaLaboratory for Immunogenetics, Central Research TB Institute, 107564 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaLaboratory for Immunogenetics, Central Research TB Institute, 107564 Moscow, RussiaLaboratory for Immunogenetics, Central Research TB Institute, 107564 Moscow, RussiaLaboratory for Immunogenetics, Central Research TB Institute, 107564 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaLaboratory for Immunogenetics, Central Research TB Institute, 107564 Moscow, RussiaThe role of neutrophils in tuberculosis infection remains less well studied compared to that of the CD4<sup>+</sup> T-lymphocytes and macrophages. Thus, alterations in <i>Mycobacterium tuberculosis</i> transcription profile following phagocytosis by neutrophils and how these shifts differ from those caused by macrophage phagocytosis remain unknown. We developed a mouse model that allows obtaining large amounts of either neutrophils or macrophages infected in vivo with <i>M. tuberculosis</i> for mycobacteria isolation in quantities sufficient for the whole genome RNA sequencing and aerosol challenge of mice. Here, we present: (i) the differences in transcription profiles of mycobacteria isolated from liquid cultures, neutrophils and macrophages infected in vivo; (ii) phenotypes of infection and lung inflammation (life span, colony forming units (CFU) counts in organs, lung pathology, immune cells infiltration and cytokine production) in genetically TB-susceptible mice identically infected via respiratory tract with neutrophil-passaged (NP), macrophage-passaged (MP) and conventionally prepared (CP) mycobacteria. Two-hour residence within neutrophils caused transcriptome shifts consistent with mycobacterial transition to dormancy and diminished their capacity to attract immune cells to infected lung tissue. Mycobacterial multiplication in organs did not depend upon pre-phagocytosis, whilst survival time of infected mice was shorter in the group infected with NP bacilli. We also discuss possible reasons for these phenotypic divergences.https://www.mdpi.com/1422-0067/23/6/2961<i>M. tuberculosis</i> transcriptomeneutrophilsmacrophagesinfection progressionimmune responsemouse model |
| spellingShingle | Elena Kondratieva Konstantin Majorov Artem Grigorov Yulia Skvortsova Tatiana Kondratieva Elvira Rubakova Irina Linge Tatyana Azhikina Alexander Apt An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host International Journal of Molecular Sciences <i>M. tuberculosis</i> transcriptome neutrophils macrophages infection progression immune response mouse model |
| title | An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host |
| title_full | An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host |
| title_fullStr | An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host |
| title_full_unstemmed | An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host |
| title_short | An In Vivo Model of Separate <i>M. tuberculosis</i> Phagocytosis by Neutrophils and Macrophages: Gene Expression Profiles in the Parasite and Disease Development in the Mouse Host |
| title_sort | in vivo model of separate i m tuberculosis i phagocytosis by neutrophils and macrophages gene expression profiles in the parasite and disease development in the mouse host |
| topic | <i>M. tuberculosis</i> transcriptome neutrophils macrophages infection progression immune response mouse model |
| url | https://www.mdpi.com/1422-0067/23/6/2961 |
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