Abstract
A significant proportion of individuals heavily exposed to infectious tuberculosis patients do not acquire Mycobacterium tuberculosis (Mtb) infection, as detected by an interferon gamma release assay (IGRA). Trained immunity may contribute to this host resistance to Mtb infection, also termed early clearance. From a prospective tuberculosis household study in Indonesia we selected 80 heavily exposed IGRA-negative household contacts, of whom 40 converted their baseline-negative IGRA to positive after three months (IGRA converters) and 40 remained IGRA-negative (early clearers). From all individuals we measured circulating β-D-glucan and used their serum for induction of trained immunity in vitro, using peripheral blood mononuclear cells from healthy unexposed Dutch donors, that were stimulated with unrelated stimuli six days after exposure to serum from household contacts. β-D-glucan concentrations and positivity did not correlate with early clearance, nor with serum-induced in-vitro trained immunity as measured by heterologous cytokine responses. These findings suggest that early clearance is unlikely to be maintained by circulating β-D-glucan or other serum factors present at exposure to Mtb, and may instead depend on cell-intrinsic or local host processes not captured by serum-based assays.