| Title: |
Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia |
| Authors: |
Setiabudiawan, TP; Apriani, L; Verrall, AJ; Utami, F; Schneider, M; Indrati, AR; Halim, PP; Kaplonek, P; Malca, H; Lee, JS; Moorlag, SJCFM; de Bree, LCJ; Mourits, VP; Joosten, LAB; Netea, MG; Alisjahbana, B; McNamara, RP; Alter, G; van Laarhoven, A; Ussher, JE; Sharples, K; Koeken, VACM; Hill, PC; van Crevel, R |
| Publisher Information: |
Nature Research |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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’. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41467-024-55501-6 |
| Availability: |
https://doi.org/10.1038/s41467-024-55501-6; https://ora.ox.ac.uk/objects/uuid:cb09118e-3ebd-4c34-872d-d4669e3c82cc |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.C307E5C7 |
| Database: |
BASE |