Lineage 2-Beijing Mycobacterium tuberculosis strains suppress BCG-trained innate immunity early after infection

Authors

Daniels, N. J., Setiabudiawan, T. P., Dutt, T. S., Hill, P. C., Henao-Tamayo, M., van Crevel, R., Kirman, J.

Abstract

Genetically distinct lineages of Mycobacterium tuberculosis differ in their virulence, transmissibility, and immune evasion capacity. The modern Lineage 2-Beijing (L2-B) clade of Mtb, which is highly prevalent in Asia and now globally distributed, is associated with resistance to the bacille Calmette Guerin (BCG) vaccine. Using a murine BCG vaccination model followed by aerosol challenge with geographically matched L2-B or Lineage 4 clinical isolates, we examined how L2-B circumvents vaccine-induced immunity. BCG-trained alveolar macrophages showed impaired control of L2-B growth in vitro. Spatial transcriptomic profiling of infected lungs revealed broad transcriptional reprogramming, including selective suppression of pathways essential for macrophage activation and trained innate immunity. Similar immune dysregulation was observed in peripheral blood from BCG-vaccinated household contacts of L2-B smear-positive TB patients. Together, these findings suggest mechanisms of lineage-specific immune evasion in TB, highlight key components of BCG-induced protection, and support re-evaluation of current TB vaccine strategies.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 02 Apr 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.