Lineage 2-Beijing Mycobacterium tuberculosis strains suppress BCG-trained innate immunity early after infection
Daniels, N. J.; Setiabudiawan, T. P.; Dutt, T. S.; Hill, P. C.; Henao-Tamayo, M.; van Crevel, R.; Kirman, J.
Show 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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates 96%
- Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+ T cells 95%
- Circulating Cell-Free RNA in Blood as a Host Response Biomarker for the Detection of Tuberculosis 95%
Similar papers in this journal
- Exposure to mycobacterium remodels alveolar macrophages and the early innate response to Mycobacterium tuberculosis infection 98%
- Single-cell profiling reveals that dynamic lung immune responses distinguish protection from susceptibility to tuberculosis 97%
- Fatty acid metabolism in neutrophils promotes lung damage and bacterial replication during tuberculosis. 96%
Similar papers in this journal
- Trained ILC2 prevent IL-17-associated lung injury during helminth infection through a serotonin-dependent mechanism 96%
- Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice 96%
- Regulatory T cells control the dynamic and site-specific polarization of CD4 T cells following Salmonella infection 95%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.