Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field
Tuberculosis (TB) remains one of the deadliest infectious diseases in the world and every 20 seconds a person dies from TB. An important attribute of human TB is induction of a granulomatous inflammation that creates a dynamic range of local microenvironments in infected organs, where the immune res...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1059725/full |
| _version_ | 1811296315234058240 |
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| author | Senait Ashenafi Senait Ashenafi Susanna Brighenti |
| author_facet | Senait Ashenafi Senait Ashenafi Susanna Brighenti |
| author_sort | Senait Ashenafi |
| collection | DOAJ |
| description | Tuberculosis (TB) remains one of the deadliest infectious diseases in the world and every 20 seconds a person dies from TB. An important attribute of human TB is induction of a granulomatous inflammation that creates a dynamic range of local microenvironments in infected organs, where the immune responses may be considerably different compared to the systemic circulation. New and improved technologies for in situ quantification and multimodal imaging of mRNA transcripts and protein expression at the single-cell level have enabled significantly improved insights into the local TB granuloma microenvironment. Here, we review the most recent data on regulation of immunity in the TB granuloma with an enhanced focus on selected in situ studies that enable spatial mapping of immune cell phenotypes and functions. We take advantage of the conceptual framework of the cancer-immunity cycle to speculate how local T cell responses may be enhanced in the granuloma microenvironment at the site of Mycobacterium tuberculosis infection. This includes an exploratory definition of “hot”, immune-inflamed, and “cold”, immune-excluded TB granulomas that does not refer to the level of bacterial replication or metabolic activity, but to the relative infiltration of T cells into the infected lesions. Finally, we reflect on the current knowledge and controversy related to reactivation of active TB in cancer patients treated with immune checkpoint inhibitors such as PD-1/PD-L1 and CTLA-4. An understanding of the underlying mechanisms involved in the induction and maintenance or disruption of immunoregulation in the TB granuloma microenvironment may provide new avenues for host-directed therapies that can support standard antibiotic treatment of persistent TB disease. |
| first_indexed | 2024-04-13T05:46:31Z |
| format | Article |
| id | doaj.art-4187dd7db230401db797d811c4108dea |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T05:46:31Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4187dd7db230401db797d811c4108dea2022-12-22T02:59:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10597251059725Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer fieldSenait Ashenafi0Senait Ashenafi1Susanna Brighenti2Department of Medicine Huddinge, Center for Infectious Medicine (CIM), Karolinska Institutet, ANA Futura, Huddinge, SwedenDepartment of Pathology, School of Medicine, College of Health Sciences, Tikur Anbessa Specialized Hospital and Addis Ababa University, Addis Ababa, EthiopiaDepartment of Medicine Huddinge, Center for Infectious Medicine (CIM), Karolinska Institutet, ANA Futura, Huddinge, SwedenTuberculosis (TB) remains one of the deadliest infectious diseases in the world and every 20 seconds a person dies from TB. An important attribute of human TB is induction of a granulomatous inflammation that creates a dynamic range of local microenvironments in infected organs, where the immune responses may be considerably different compared to the systemic circulation. New and improved technologies for in situ quantification and multimodal imaging of mRNA transcripts and protein expression at the single-cell level have enabled significantly improved insights into the local TB granuloma microenvironment. Here, we review the most recent data on regulation of immunity in the TB granuloma with an enhanced focus on selected in situ studies that enable spatial mapping of immune cell phenotypes and functions. We take advantage of the conceptual framework of the cancer-immunity cycle to speculate how local T cell responses may be enhanced in the granuloma microenvironment at the site of Mycobacterium tuberculosis infection. This includes an exploratory definition of “hot”, immune-inflamed, and “cold”, immune-excluded TB granulomas that does not refer to the level of bacterial replication or metabolic activity, but to the relative infiltration of T cells into the infected lesions. Finally, we reflect on the current knowledge and controversy related to reactivation of active TB in cancer patients treated with immune checkpoint inhibitors such as PD-1/PD-L1 and CTLA-4. An understanding of the underlying mechanisms involved in the induction and maintenance or disruption of immunoregulation in the TB granuloma microenvironment may provide new avenues for host-directed therapies that can support standard antibiotic treatment of persistent TB disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1059725/fulltuberculosisMycobacterium tuberculosisgranulomaimmunitymacrophageT cell |
| spellingShingle | Senait Ashenafi Senait Ashenafi Susanna Brighenti Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field Frontiers in Immunology tuberculosis Mycobacterium tuberculosis granuloma immunity macrophage T cell |
| title | Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field |
| title_full | Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field |
| title_fullStr | Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field |
| title_full_unstemmed | Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field |
| title_short | Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field |
| title_sort | reinventing the human tuberculosis tb granuloma learning from the cancer field |
| topic | tuberculosis Mycobacterium tuberculosis granuloma immunity macrophage T cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1059725/full |
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