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

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.

Pulmonary responses to pathogen-specific antigens in latent Mycobacterium tuberculosis infection.

In this study, we used ELISPOT to quantify frequencies of bronchoalveolar lavage (BAL) and peripheral blood T cells capable of producing IFNγ in response to PPD, antigen 85B, and Mtb-specific antigens CFP-10 and ESAT-6 in individuals with latent tuberculosis infection (LTBI) and Mtb-naïve controls. Compared to peripheral blood, BAL cells of LTBI subjects displayed significant enrichment for T cells responding to PPD, antigen 85B, and CFP-10, but not to ESAT-6. Baseline BAL cells of LTBI subjects displayed significant production of Mig (CXCL9) in response to PPD, antigen 85B, and CFP-10 as well. These findings suggest that enrichment for Mtb-specific T cells within BAL is not unique to active pulmonary tuberculosis and may, to the contrary, contribute to protection from re-infection in Mtb immune individuals.