Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot Study
A granuloma, a pathologic hallmark of tuberculosis (TB), is a complex cellular structure that develops at the site of <i>Mycobacterium tuberculosis</i> (Mtb) infection and is comprised of different immune cell types. Severe pulmonary TB in humans is characterized by the presence of heter...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Journal of Respiration |
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| Online Access: | https://www.mdpi.com/2673-527X/1/4/23 |
| _version_ | 1797503179950129152 |
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| author | Ranjeet Kumar Selvakumar Subbian |
| author_facet | Ranjeet Kumar Selvakumar Subbian |
| author_sort | Ranjeet Kumar |
| collection | DOAJ |
| description | A granuloma, a pathologic hallmark of tuberculosis (TB), is a complex cellular structure that develops at the site of <i>Mycobacterium tuberculosis</i> (Mtb) infection and is comprised of different immune cell types. Severe pulmonary TB in humans is characterized by the presence of heterogeneous granulomas, ranging from highly cellular to solid/non-necrotic and necrotic lesions, within the lungs. The host-Mtb interactions within the granulomas dictate the containment of Mtb infection or its progression into a necrotic, cavitary disease. However, the immune environment in various granulomas is poorly understood. The myeloid-derived suppressor cells (MDSCs) are key immune cells that regulate the protective versus permissive host responses against Mtb infection. However, their contexture within the lung granulomas remains unclear. In this study, using single and multiplex immunohistochemical staining, we analyzed the distribution of MDSCs, macrophages, CD4+ T cells and their immunometabolic and effector function states in the solid/non-necrotic and necrotic granulomas in patients with active pulmonary TB. We found increased MDSCs with elevated expression of immunosuppressive molecules in the solid/non-necrotic granulomas. In contrast, cells in the solid and necrotic granulomas produced similar levels of IL-6 and IL-10. Our findings suggest that MDSCs are present in solid/non-necrotic granuloma, which may play an essential role in the progression into a necrotic lesion, thus exacerbating disease pathology and transmission. |
| first_indexed | 2024-03-10T03:46:50Z |
| format | Article |
| id | doaj.art-5e53c4da615c413883120b3c1be5bd24 |
| institution | Directory Open Access Journal |
| issn | 2673-527X |
| language | English |
| last_indexed | 2024-03-10T03:46:50Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Respiration |
| spelling | doaj.art-5e53c4da615c413883120b3c1be5bd242023-11-23T09:06:24ZengMDPI AGJournal of Respiration2673-527X2021-10-011424825910.3390/jor1040023Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot StudyRanjeet Kumar0Selvakumar Subbian1The Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USAThe Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USAA granuloma, a pathologic hallmark of tuberculosis (TB), is a complex cellular structure that develops at the site of <i>Mycobacterium tuberculosis</i> (Mtb) infection and is comprised of different immune cell types. Severe pulmonary TB in humans is characterized by the presence of heterogeneous granulomas, ranging from highly cellular to solid/non-necrotic and necrotic lesions, within the lungs. The host-Mtb interactions within the granulomas dictate the containment of Mtb infection or its progression into a necrotic, cavitary disease. However, the immune environment in various granulomas is poorly understood. The myeloid-derived suppressor cells (MDSCs) are key immune cells that regulate the protective versus permissive host responses against Mtb infection. However, their contexture within the lung granulomas remains unclear. In this study, using single and multiplex immunohistochemical staining, we analyzed the distribution of MDSCs, macrophages, CD4+ T cells and their immunometabolic and effector function states in the solid/non-necrotic and necrotic granulomas in patients with active pulmonary TB. We found increased MDSCs with elevated expression of immunosuppressive molecules in the solid/non-necrotic granulomas. In contrast, cells in the solid and necrotic granulomas produced similar levels of IL-6 and IL-10. Our findings suggest that MDSCs are present in solid/non-necrotic granuloma, which may play an essential role in the progression into a necrotic lesion, thus exacerbating disease pathology and transmission.https://www.mdpi.com/2673-527X/1/4/23granulomaimmune celltuberculosisMDSCcavitypulmonary |
| spellingShingle | Ranjeet Kumar Selvakumar Subbian Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot Study Journal of Respiration granuloma immune cell tuberculosis MDSC cavity pulmonary |
| title | Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot Study |
| title_full | Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot Study |
| title_fullStr | Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot Study |
| title_full_unstemmed | Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot Study |
| title_short | Immune Correlates of Non-Necrotic and Necrotic Granulomas in Pulmonary Tuberculosis: A Pilot Study |
| title_sort | immune correlates of non necrotic and necrotic granulomas in pulmonary tuberculosis a pilot study |
| topic | granuloma immune cell tuberculosis MDSC cavity pulmonary |
| url | https://www.mdpi.com/2673-527X/1/4/23 |
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