Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity
IntroductionDuring infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune r...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1211404/full |
| _version_ | 1797805695436849152 |
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| author | Ana Raquel Maceiras Ana Raquel Maceiras Diogo Silvério Diogo Silvério Rute Gonçalves Rute Gonçalves Marcos S. Cardoso Margarida Saraiva Margarida Saraiva |
| author_facet | Ana Raquel Maceiras Ana Raquel Maceiras Diogo Silvério Diogo Silvério Rute Gonçalves Rute Gonçalves Marcos S. Cardoso Margarida Saraiva Margarida Saraiva |
| author_sort | Ana Raquel Maceiras |
| collection | DOAJ |
| description | IntroductionDuring infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and Mycobacterium tuberculosis may colonize the BM, studies using the mouse model of infection and the laboratory reference strain M. tuberculosis H37Rv have demonstrated limited emergency myelopoiesis and trained immunity.MethodsTo further address this issue, we aerosol- infected C57BL/6 mice with high doses of the hypervirulent M. tuberculosis isolate HN878 and monitored alterations to the BM. This experimental model better resembles the human blood immune signature of TB.Results and discussionWe found increased frequencies of lineage-Sca-1+cKit+ (LSK) cells and the granulocyte/macrophage progenitor (GMP) population. At the mature cell level, we observed an increase of monocytes and neutrophils in the blood and lung, likely reflecting the increased BM myeloid output. Monocytes or monocyte-derived macrophages recovered from the BM of M. tuberculosis HN878-infected mice did not show signs of trained immunity, suggesting an uncoupling of emergency myelopoiesis and trained immunity in the BM. Surprisingly, M. tuberculosis HN878-induced emergency myelopoiesis was not fully dependent on IFNγ, as mice lacking this cytokine and infected under the same conditions as wild-type mice still presented BM alterations. These data expand our understanding of the immune response to M. tuberculosis and raise awareness of pathogen strain-imposed differences to host responses. |
| first_indexed | 2024-03-13T05:54:51Z |
| format | Article |
| id | doaj.art-686b33d356644822805736b57016b27d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T05:54:51Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-686b33d356644822805736b57016b27d2023-06-13T06:09:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.12114041211404Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunityAna Raquel Maceiras0Ana Raquel Maceiras1Diogo Silvério2Diogo Silvério3Rute Gonçalves4Rute Gonçalves5Marcos S. Cardoso6Margarida Saraiva7Margarida Saraiva8Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, PortugalInstituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, PortugalDoctoral Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, PortugalDoctoral Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, PortugalInstituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, PortugalIntroductionDuring infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and Mycobacterium tuberculosis may colonize the BM, studies using the mouse model of infection and the laboratory reference strain M. tuberculosis H37Rv have demonstrated limited emergency myelopoiesis and trained immunity.MethodsTo further address this issue, we aerosol- infected C57BL/6 mice with high doses of the hypervirulent M. tuberculosis isolate HN878 and monitored alterations to the BM. This experimental model better resembles the human blood immune signature of TB.Results and discussionWe found increased frequencies of lineage-Sca-1+cKit+ (LSK) cells and the granulocyte/macrophage progenitor (GMP) population. At the mature cell level, we observed an increase of monocytes and neutrophils in the blood and lung, likely reflecting the increased BM myeloid output. Monocytes or monocyte-derived macrophages recovered from the BM of M. tuberculosis HN878-infected mice did not show signs of trained immunity, suggesting an uncoupling of emergency myelopoiesis and trained immunity in the BM. Surprisingly, M. tuberculosis HN878-induced emergency myelopoiesis was not fully dependent on IFNγ, as mice lacking this cytokine and infected under the same conditions as wild-type mice still presented BM alterations. These data expand our understanding of the immune response to M. tuberculosis and raise awareness of pathogen strain-imposed differences to host responses.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1211404/fulltuberculosismyelopoiesistrained immunityinterferon-gammabone marrow |
| spellingShingle | Ana Raquel Maceiras Ana Raquel Maceiras Diogo Silvério Diogo Silvério Rute Gonçalves Rute Gonçalves Marcos S. Cardoso Margarida Saraiva Margarida Saraiva Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity Frontiers in Immunology tuberculosis myelopoiesis trained immunity interferon-gamma bone marrow |
| title | Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity |
| title_full | Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity |
| title_fullStr | Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity |
| title_full_unstemmed | Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity |
| title_short | Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity |
| title_sort | infection with hypervirulent mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity |
| topic | tuberculosis myelopoiesis trained immunity interferon-gamma bone marrow |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1211404/full |
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