Distinct gene expression signatures comparing latent tuberculosis infection with different routes of Bacillus Calmette-Guerin vaccination
12/2023
Journal Article
Authors:
Silver, R. F.;
Xia, M.;
Storer, C. E.;
Jarvela, J. R.;
Moyer, M. C.;
Blazevic, A.;
Stoeckel, D. A.;
Rakey, E. K.;
Tennant, J. M.;
Goll, J. B.;
Head, R. D.;
Hoft, D. F.
Volume:
14
Pagination:
8507
Issue:
1
Journal:
Nat Commun
PMID:
38129388
URL:
https://www.ncbi.nlm.nih.gov/pubmed/38129388
DOI:
10.1038/s41467-023-44136-8
Keywords:
Humans
Latent Tuberculosis
BCG Vaccine
*Mycobacterium tuberculosis/genetics
Transcriptome
*Tuberculosis/prevention & control
Vaccination
*Mycobacterium bovis
Abstract:
Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guerin (BCG); this may reflect the inability of intradermal vaccination to optimally induce pulmonary immunity. In contrast, respiratory Mycobacterium tuberculosis infection usually results in the immune-mediated bacillary containment of latent tuberculosis infection (LTBI). Here we present RNA-Seq-based assessments of systemic and pulmonary immune cells from LTBI participants and recipients of intradermal and oral BCG. LTBI individuals uniquely display ongoing immune activation and robust CD4 T cell recall responses in blood and lung. Intradermal BCG is associated with robust systemic immunity but only limited pulmonary immunity. Conversely, oral BCG induces limited systemic immunity but distinct pulmonary responses including enhanced inflammasome activation potentially associated with mucosal-associated invariant T cells. Further, IL-9 is identified as a component of systemic immunity in LTBI and intradermal BCG, and pulmonary immunity following oral BCG.
