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

Nature communications

Authors: 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

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'.

© 2024. The Author(s).

PMID: 39747050

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