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Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia

Setiabudiawan, T. P.; Apriani, L.; Verrall, A. J.; Utami, F.; Schneider, M.; Indrati, A. R.; Halim, P. P.; Kaplonek, P.; Malca, H.; Shih-Lu Lee, J.; Moorlag, S. J.; de Bree, L. C. J.; Mourits, V. P.; Joosten, L. A.; Netea, M. G.; Alisjahbana, B.; McNamara, R. P.; Alter, G.; van Laarhoven, A.; Ussher, J.; Sharples, K.; Koeken, V. A.; Hill, P. C.; van Crevel, R.

2024-06-21 immunology
10.1101/2024.06.21.599883 bioRxiv
Show 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-{gamma}-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 BCG-vaccinated individuals - 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.

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