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

Ahmed, A and Tripathi, H and van Meijgaarden, KE and Kumar, NC and Adiga, V and Rakshit, S and Parthiban, C and Eveline J, S and D'Souza, G and Dias, M and Ottenhoff, THM and Netea, MG and Joosten, SA and Vyakarnam, A (2023) BCG revaccination in adults enhances pro-inflammatory markers of trained immunity along with anti-inflammatory pathways. In: iScience, 26 (10).

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Abstract

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−CD14hi 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−CD14hi 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. © 2023

Item Type:	Journal Article
Publication:	iScience
Publisher:	Elsevier Inc.
Additional Information:	The copyright for this article belongs to the Elsevier Inc.
Department/Centre:	Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited:	01 Dec 2023 03:57
Last Modified:	01 Dec 2023 03:57
URI:	https://eprints.iisc.ac.in/id/eprint/83388

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