T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques
Summary: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. Here, we identify...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722005976 |
| _version_ | 1818211532244254720 |
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| author | Nicole L. Grant Pauline Maiello Edwin Klein Philana Ling Lin H. Jacob Borish Jaime Tomko L. James Frye Alexander G. White Denise E. Kirschner Joshua T. Mattila JoAnne L. Flynn |
| author_facet | Nicole L. Grant Pauline Maiello Edwin Klein Philana Ling Lin H. Jacob Borish Jaime Tomko L. James Frye Alexander G. White Denise E. Kirschner Joshua T. Mattila JoAnne L. Flynn |
| author_sort | Nicole L. Grant |
| collection | DOAJ |
| description | Summary: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. Here, we identify and compare the pathological, cellular, and functional differences in granulomas at 4, 12, and 20 weeks post-infection in Chinese cynomolgus macaques. Original granulomas differ in transcription-factor expression within adaptive lymphocytes, with those at 12 weeks showing higher frequencies of CD8+T-bet+ T cells, while CD4+T-bet+ T cells increase at 20 weeks post-infection. The appearance of T-bet+ adaptive T cells at 12 and 20 weeks is coincident with a reduction in bacterial burden, suggesting their critical role in Mtb control. This study highlights the evolution of T cell responses within lung granulomas, suggesting that vaccines promoting the development and migration of T-bet+ T cells would enhance mycobacterial control. |
| first_indexed | 2024-12-12T05:34:00Z |
| format | Article |
| id | doaj.art-27d79ee8867c4472a720d0e7466b5302 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T05:34:00Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-27d79ee8867c4472a720d0e7466b53022022-12-22T00:36:13ZengElsevierCell Reports2211-12472022-05-01397110826T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaquesNicole L. Grant0Pauline Maiello1Edwin Klein2Philana Ling Lin3H. Jacob Borish4Jaime Tomko5L. James Frye6Alexander G. White7Denise E. Kirschner8Joshua T. Mattila9JoAnne L. Flynn10Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USADivision of Laboratory Animal Research, University of Pittsburgh, Pittsburgh, PA, USADepartment of Pediatrics, Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USADepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Corresponding authorSummary: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. Here, we identify and compare the pathological, cellular, and functional differences in granulomas at 4, 12, and 20 weeks post-infection in Chinese cynomolgus macaques. Original granulomas differ in transcription-factor expression within adaptive lymphocytes, with those at 12 weeks showing higher frequencies of CD8+T-bet+ T cells, while CD4+T-bet+ T cells increase at 20 weeks post-infection. The appearance of T-bet+ adaptive T cells at 12 and 20 weeks is coincident with a reduction in bacterial burden, suggesting their critical role in Mtb control. This study highlights the evolution of T cell responses within lung granulomas, suggesting that vaccines promoting the development and migration of T-bet+ T cells would enhance mycobacterial control.http://www.sciencedirect.com/science/article/pii/S2211124722005976CP: ImmunologyCP: Microbiology |
| spellingShingle | Nicole L. Grant Pauline Maiello Edwin Klein Philana Ling Lin H. Jacob Borish Jaime Tomko L. James Frye Alexander G. White Denise E. Kirschner Joshua T. Mattila JoAnne L. Flynn T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques Cell Reports CP: Immunology CP: Microbiology |
| title | T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques |
| title_full | T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques |
| title_fullStr | T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques |
| title_full_unstemmed | T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques |
| title_short | T cell transcription factor expression evolves over time in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques |
| title_sort | t cell transcription factor expression evolves over time in granulomas from mycobacterium tuberculosis infected cynomolgus macaques |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722005976 |
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