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Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity

INTRODUCTION: During 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...

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Autores principales: Maceiras, Ana Raquel, Silvério, Diogo, Gonçalves, Rute, Cardoso, Marcos S., Saraiva, Margarida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296772/
https://www.ncbi.nlm.nih.gov/pubmed/37383236
http://dx.doi.org/10.3389/fimmu.2023.1211404
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author Maceiras, Ana Raquel
Silvério, Diogo
Gonçalves, Rute
Cardoso, Marcos S.
Saraiva, Margarida
author_facet Maceiras, Ana Raquel
Silvério, Diogo
Gonçalves, Rute
Cardoso, Marcos S.
Saraiva, Margarida
author_sort Maceiras, Ana Raquel
collection PubMed
description INTRODUCTION: During 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. METHODS: To 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 DISCUSSION: We 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.
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spelling pubmed-102967722023-06-28 Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity Maceiras, Ana Raquel Silvério, Diogo Gonçalves, Rute Cardoso, Marcos S. Saraiva, Margarida Front Immunol Immunology INTRODUCTION: During 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. METHODS: To 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 DISCUSSION: We 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. Frontiers Media S.A. 2023-06-13 /pmc/articles/PMC10296772/ /pubmed/37383236 http://dx.doi.org/10.3389/fimmu.2023.1211404 Text en Copyright © 2023 Maceiras, Silvério, Gonçalves, Cardoso and Saraiva https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Maceiras, Ana Raquel
Silvério, Diogo
Gonçalves, Rute
Cardoso, Marcos S.
Saraiva, Margarida
Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296772/
https://www.ncbi.nlm.nih.gov/pubmed/37383236
http://dx.doi.org/10.3389/fimmu.2023.1211404
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