Distinct gene expression signatures comparing latent tuberculosis infection with different routes of Bacillus Calmette-Guérin vaccination

Richard F. Silver (), Mei Xia, Chad E. Storer, Jessica R. Jarvela, Michelle C. Moyer, Azra Blazevic, David A. Stoeckel, Erin K. Rakey, Jan M. Tennant, Johannes B. Goll, Richard D. Head and Daniel F. Hoft ()
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Richard F. Silver: Case Western Reserve University School of Medicine
Mei Xia: Saint Louis University School of Medicine
Chad E. Storer: Washington University School of Medicine
Jessica R. Jarvela: Case Western Reserve University School of Medicine
Michelle C. Moyer: Case Western Reserve University School of Medicine
Azra Blazevic: Saint Louis University School of Medicine
David A. Stoeckel: Saint Louis University School of Medicine
Erin K. Rakey: Saint Louis University School of Medicine
Jan M. Tennant: Saint Louis University School of Medicine
Johannes B. Goll: Emmes Corporation
Richard D. Head: Washington University School of Medicine
Daniel F. Hoft: Saint Louis University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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 Guérin (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.

Date: 2023
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DOI: 10.1038/s41467-023-44136-8

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