BCG revaccination in adults enhances pro-inflammatory markers of trained immunity along with anti-inflammatory pathways

Ahmed, A.; Tripathi, H.; Meijgaarden, K.E.V.; Kumar, N.C.; Adiga, V.; Rakshit, S.; ... ; Vyakarnam, A. (2023)

Article / Letter to editor

This study characterized mechanisms of Bacille Calmette-Guérin (BCG) revaccination-induced trained immunity (TI) in India. Adults, BCG vaccinated at birth, were sampled longitudinally before and after a second BCG dose. BCG revaccination significantly elevated tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 in HLA-DR⁺CD16⁻CD14^hi monocytes, demonstrating induction of TI. Mycobacteria-specific CD4⁺ T cell interferon (IFN) γ, IL-2, and TNF-α were significantly higher in re-vaccinees and correlated positively with HLA-DR⁺CD16⁻CD14^hi TI responses. This, however, did not translate into increased mycobacterial growth control, measured by mycobacterial growth inhibition assay (MGIA). Post revaccination, elevated secreted TNF-α, IL-1β, and IL-6 to “heterologous” fungal, bacterial, and enhanced CXCL-10 and IFNα to viral stimuli were also observed concomitant with increased anti-inflammatory cytokine, IL-1RA. RNA sequencing after revaccination highlighted a BCG and LPS induced signature which included upregulated IL17 and TNF pathway genes and downregulated key inflammatory genes: CXCL11, CCL24, HLADRA, CTSS, CTSC. Our data highlight a balanced immune response comprising pro- and anti-inflammatory mediators to be a feature of BCG revaccination-induced immunity.

• All authors: Ahmed, A.; Tripathi, H.; Meijgaarden, K.E.V.; Kumar, N.C.; Adiga, V.; Rakshit, S.; Parthiban, C.; Eveline, J.S.; D'Souza, G.; Dias, M.; Ottenhoff, T.H.M.; Netea, M.G.; Joosten, S.A.; Vyakarnam, A.
• Date: 2023-09-27
• Journal: iScience
• Volume: 26
• Issue: 10
• DOI: doi:10.1016/j.isci.2023.107889
• Link: https://www.sciencedirect.com/science/article/pii/S2589004223019661?via%...