Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia
Abstract Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response c...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55501-6 |
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| author | Todia P. Setiabudiawan Lika Apriani Ayesha J. Verrall Fitria Utami Marion Schneider Agnes R. Indrati Pauline P. Halim Paulina Kaplonek Hadar Malca Jessica Shih-Lu Lee Simone J. C. F. M. Moorlag L. Charlotte J. de Bree Vera P. Mourits Leo A. B. Joosten Mihai G. Netea Bachti Alisjahbana Ryan P. McNamara Galit Alter Arjan van Laarhoven James E. Ussher Katrina Sharples Valerie A. C. M. Koeken Philip C. Hill Reinout van Crevel |
| author_facet | Todia P. Setiabudiawan Lika Apriani Ayesha J. Verrall Fitria Utami Marion Schneider Agnes R. Indrati Pauline P. Halim Paulina Kaplonek Hadar Malca Jessica Shih-Lu Lee Simone J. C. F. M. Moorlag L. Charlotte J. de Bree Vera P. Mourits Leo A. B. Joosten Mihai G. Netea Bachti Alisjahbana Ryan P. McNamara Galit Alter Arjan van Laarhoven James E. Ussher Katrina Sharples Valerie A. C. M. Koeken Philip C. Hill Reinout van Crevel |
| author_sort | Todia P. Setiabudiawan |
| collection | DOAJ |
| description | Abstract Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube. Neither circulating concentrations of Mtb-specific antibodies nor functional antibody activity associated with IGRA status at baseline or follow-up. In a cohort of adults in a low tuberculosis incidence setting, BCG vaccination induced heterologous innate cytokine production, but only marginally affected Mtb-specific antibody profiles. Our findings suggest that a more efficient host innate immune response, rather than a humoral response, mediates early clearance of Mtb. The protective effect of BCG vaccination against Mtb infection may be linked to innate immune priming, also termed ‘trained immunity’. |
| format | Article |
| id | doaj-art-084e2e749fc14ad783240e6bc07c3f47 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-084e2e749fc14ad783240e6bc07c3f472025-01-05T12:38:03ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-024-55501-6Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in IndonesiaTodia P. Setiabudiawan0Lika Apriani1Ayesha J. Verrall2Fitria Utami3Marion Schneider4Agnes R. Indrati5Pauline P. Halim6Paulina Kaplonek7Hadar Malca8Jessica Shih-Lu Lee9Simone J. C. F. M. Moorlag10L. Charlotte J. de Bree11Vera P. Mourits12Leo A. B. Joosten13Mihai G. Netea14Bachti Alisjahbana15Ryan P. McNamara16Galit Alter17Arjan van Laarhoven18James E. Ussher19Katrina Sharples20Valerie A. C. M. Koeken21Philip C. Hill22Reinout van Crevel23Department of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterResearch Center for Care and Control of Infectious Diseases, Universitas PadjadjaranDepartment of Pathology and Molecular Medicine, University of OtagoResearch Center for Care and Control of Infectious Diseases, Universitas PadjadjaranDepartment of Microbiology and Immunology, University of OtagoDepartment of Clinical Pathology, Faculty of Medicine, Universitas PadjadjaranFaculty of Medicine, Universitas IndonesiaRagon Institute of Mass General, MIT, and HarvardRagon Institute of Mass General, MIT, and HarvardRagon Institute of Mass General, MIT, and HarvardDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterResearch Center for Care and Control of Infectious Diseases, Universitas PadjadjaranRagon Institute of Mass General, MIT, and HarvardRagon Institute of Mass General, MIT, and HarvardDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterDepartment of Microbiology and Immunology, University of OtagoDepartment of Mathematics and Statistics, University of OtagoDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterCentre for International Health, University of OtagoDepartment of Internal Medicine and Radboud Community for Infectious Diseases (RCI), Radboud University Medical CenterAbstract Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube. Neither circulating concentrations of Mtb-specific antibodies nor functional antibody activity associated with IGRA status at baseline or follow-up. In a cohort of adults in a low tuberculosis incidence setting, BCG vaccination induced heterologous innate cytokine production, but only marginally affected Mtb-specific antibody profiles. Our findings suggest that a more efficient host innate immune response, rather than a humoral response, mediates early clearance of Mtb. The protective effect of BCG vaccination against Mtb infection may be linked to innate immune priming, also termed ‘trained immunity’.https://doi.org/10.1038/s41467-024-55501-6 |
| spellingShingle | Todia P. Setiabudiawan Lika Apriani Ayesha J. Verrall Fitria Utami Marion Schneider Agnes R. Indrati Pauline P. Halim Paulina Kaplonek Hadar Malca Jessica Shih-Lu Lee Simone J. C. F. M. Moorlag L. Charlotte J. de Bree Vera P. Mourits Leo A. B. Joosten Mihai G. Netea Bachti Alisjahbana Ryan P. McNamara Galit Alter Arjan van Laarhoven James E. Ussher Katrina Sharples Valerie A. C. M. Koeken Philip C. Hill Reinout van Crevel Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia Nature Communications |
| title | Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia |
| title_full | Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia |
| title_fullStr | Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia |
| title_full_unstemmed | Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia |
| title_short | Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia |
| title_sort | immune correlates of early clearance of mycobacterium tuberculosis among tuberculosis household contacts in indonesia |
| url | https://doi.org/10.1038/s41467-024-55501-6 |
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