Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies
The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacteria...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/10/12/1572 |
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| author | Robert E. Brown Robert L. Hunter |
| author_facet | Robert E. Brown Robert L. Hunter |
| author_sort | Robert E. Brown |
| collection | DOAJ |
| description | The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Bacteria grow massively on the cavity wall where they can be coughed out to infect new people. Here we extend these findings with the demonstration of secreted mycobacterial antigens, but not acid fast bacilli (AFB) of <i>M. tuberculosis</i> in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas, and fibrocaseous disease. |
| first_indexed | 2024-03-10T03:22:23Z |
| format | Article |
| id | doaj.art-5807119b50c54ed8894fac9a2663a30b |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T03:22:23Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-5807119b50c54ed8894fac9a2663a30b2023-11-23T10:00:51ZengMDPI AGPathogens2076-08172021-12-011012157210.3390/pathogens10121572Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed TherapiesRobert E. Brown0Robert L. Hunter1Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USADepartment of Pathology and Laboratory Medicine, University of Texas Health Sciences Center at Houston, Houston, TX 77030, USAThe characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Bacteria grow massively on the cavity wall where they can be coughed out to infect new people. Here we extend these findings with the demonstration of secreted mycobacterial antigens, but not acid fast bacilli (AFB) of <i>M. tuberculosis</i> in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas, and fibrocaseous disease.https://www.mdpi.com/2076-0817/10/12/1572tuberculosissecretory antigensbronchiolar epitheliumalveolar pneumocytesM2 polarizationCOX-2 |
| spellingShingle | Robert E. Brown Robert L. Hunter Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies Pathogens tuberculosis secretory antigens bronchiolar epithelium alveolar pneumocytes M2 polarization COX-2 |
| title | Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies |
| title_full | Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies |
| title_fullStr | Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies |
| title_full_unstemmed | Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies |
| title_short | Early Lesion of Post-Primary Tuberculosis: Subclinical Driver of Disease and Target for Vaccines and Host-Directed Therapies |
| title_sort | early lesion of post primary tuberculosis subclinical driver of disease and target for vaccines and host directed therapies |
| topic | tuberculosis secretory antigens bronchiolar epithelium alveolar pneumocytes M2 polarization COX-2 |
| url | https://www.mdpi.com/2076-0817/10/12/1572 |
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