Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosis
The BCG vaccine has been used against tuberculosis (TB) for over a hundred years; however, it does not protect adults from pulmonary TB. To develop alternative vaccines against TB, we generated Mycobacterium tuberculosis H37Rv (Mtb)-derived vaccine strains by rationally deleting key virulent genes,...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1583439/full |
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| author | Raja Veerapandian Barbara Yang Areanna Carmona Melina J. Sedano Victoria Reid Victoria Reid Rodrigo Jimenez Rodrigo Jimenez Jessica Chacon Chinnaswamy Jagannath Enrique I. Ramos Enrique I. Ramos Shrikanth S. Gadad Shrikanth S. Gadad Subramanian Dhandayuthapani Subramanian Dhandayuthapani |
| author_facet | Raja Veerapandian Barbara Yang Areanna Carmona Melina J. Sedano Victoria Reid Victoria Reid Rodrigo Jimenez Rodrigo Jimenez Jessica Chacon Chinnaswamy Jagannath Enrique I. Ramos Enrique I. Ramos Shrikanth S. Gadad Shrikanth S. Gadad Subramanian Dhandayuthapani Subramanian Dhandayuthapani |
| author_sort | Raja Veerapandian |
| collection | DOAJ |
| description | The BCG vaccine has been used against tuberculosis (TB) for over a hundred years; however, it does not protect adults from pulmonary TB. To develop alternative vaccines against TB, we generated Mycobacterium tuberculosis H37Rv (Mtb)-derived vaccine strains by rationally deleting key virulent genes, resulting in single (SKO; ΔfbpA), double (DKO; ΔfbpA-ΔsapM), triple (TKO-D; ΔfbpA-ΔsapM-ΔdosR and TKO-Z; ΔfbpA-ΔsapM-Δzmp1), and quadruple (QKO; ΔfbpA-ΔsapM-Δzmp1-dosR) strains. To understand how macrophages, the host cells that defend against infection and process antigens for presentation to immune cells, respond to these vaccine strains, we performed transcriptomic analyses of mouse bone marrow-derived macrophages (BMDMs) infected with these strains. The transcriptomic data were compared with similar data obtained from macrophages infected with Mtb H37Rv and BCG. Our analyses revealed that genes associated with various immune and cell signaling pathways, such as NF-kappa B signaling, TNF signaling, cytokine-cytokine receptor interaction, chemokine signaling, hematopoietic cell lineage, Toll-like receptor signaling, IL-17 signaling, Th1 and Th2 cell differentiation, Th17 cell differentiation, and T cell receptor signaling were differentially expressed in BMDMs infected with our vaccine strains. Enhanced expression of cytokines and chemokines, including proinflammatory cytokines such as TNF-α, IL-6, GM-CSF, and IL-1, which are essential for the immune response against Mtb infection, was also observed in BMDMs infected with these strains. In particular, BMDMs infected with all vaccine strains exhibited a significant upregulation of genes associated with the IL-17 pathway. These results may indicate that our vaccine strains could induce a protective immune response against TB. |
| format | Article |
| id | doaj-art-96ae53c29686486e81a6772394fb0e85 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-96ae53c29686486e81a6772394fb0e852025-08-20T03:28:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15834391583439Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosisRaja Veerapandian0Barbara Yang1Areanna Carmona2Melina J. Sedano3Victoria Reid4Victoria Reid5Rodrigo Jimenez6Rodrigo Jimenez7Jessica Chacon8Chinnaswamy Jagannath9Enrique I. Ramos10Enrique I. Ramos11Shrikanth S. Gadad12Shrikanth S. Gadad13Subramanian Dhandayuthapani14Subramanian Dhandayuthapani15Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesCenter of Emphasis in Cancer, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesCenter of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesCenter of Emphasis in Cancer, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesCenter of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesCenter of Emphasis in Cancer, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesCenter of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesFrederick L. Francis School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesDepartment of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesDepartment of Pathology and Genomic Medicine, Houston Methodist Research Institute & Weill Cornell Medical College, Houston, TX, United StatesCenter of Emphasis in Cancer, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesDepartment of Biology, University of Texas El Paso, El Paso, TX, United StatesCenter of Emphasis in Cancer, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesFrederick L. Francis School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesCenter of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesFrederick L. Francis School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United StatesThe BCG vaccine has been used against tuberculosis (TB) for over a hundred years; however, it does not protect adults from pulmonary TB. To develop alternative vaccines against TB, we generated Mycobacterium tuberculosis H37Rv (Mtb)-derived vaccine strains by rationally deleting key virulent genes, resulting in single (SKO; ΔfbpA), double (DKO; ΔfbpA-ΔsapM), triple (TKO-D; ΔfbpA-ΔsapM-ΔdosR and TKO-Z; ΔfbpA-ΔsapM-Δzmp1), and quadruple (QKO; ΔfbpA-ΔsapM-Δzmp1-dosR) strains. To understand how macrophages, the host cells that defend against infection and process antigens for presentation to immune cells, respond to these vaccine strains, we performed transcriptomic analyses of mouse bone marrow-derived macrophages (BMDMs) infected with these strains. The transcriptomic data were compared with similar data obtained from macrophages infected with Mtb H37Rv and BCG. Our analyses revealed that genes associated with various immune and cell signaling pathways, such as NF-kappa B signaling, TNF signaling, cytokine-cytokine receptor interaction, chemokine signaling, hematopoietic cell lineage, Toll-like receptor signaling, IL-17 signaling, Th1 and Th2 cell differentiation, Th17 cell differentiation, and T cell receptor signaling were differentially expressed in BMDMs infected with our vaccine strains. Enhanced expression of cytokines and chemokines, including proinflammatory cytokines such as TNF-α, IL-6, GM-CSF, and IL-1, which are essential for the immune response against Mtb infection, was also observed in BMDMs infected with these strains. In particular, BMDMs infected with all vaccine strains exhibited a significant upregulation of genes associated with the IL-17 pathway. These results may indicate that our vaccine strains could induce a protective immune response against TB.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1583439/fullMtb-vaccinesBCGmousemacrophagesRNA-sequencingtranscripts |
| spellingShingle | Raja Veerapandian Barbara Yang Areanna Carmona Melina J. Sedano Victoria Reid Victoria Reid Rodrigo Jimenez Rodrigo Jimenez Jessica Chacon Chinnaswamy Jagannath Enrique I. Ramos Enrique I. Ramos Shrikanth S. Gadad Shrikanth S. Gadad Subramanian Dhandayuthapani Subramanian Dhandayuthapani Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosis Frontiers in Immunology Mtb-vaccines BCG mouse macrophages RNA-sequencing transcripts |
| title | Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosis |
| title_full | Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosis |
| title_fullStr | Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosis |
| title_full_unstemmed | Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosis |
| title_short | Comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of Mycobacterium tuberculosis |
| title_sort | comparative transcriptomic analysis of mouse macrophages infected with live attenuated vaccine strains of mycobacterium tuberculosis |
| topic | Mtb-vaccines BCG mouse macrophages RNA-sequencing transcripts |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1583439/full |
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