Tuberculosis (Edinb). 2025 Apr 23;153:102641. doi: 10.1016/j.tube.2025.102641. Online ahead of print.
ABSTRACT
Tuberculosis (TB) is the leading cause of death due to a pathogen. The live-attenuated BCG vaccine is the only approved vaccine to prevent TB, but it fails to confer long-term protection. We hypothesize that the immunosuppressive cytokine IL-27 may contribute to the inefficacies of the BCG vaccine. IL-27 is elevated in neonates, the population most commonly administered BCG, and levels increase further upon vaccination. IL-27 interferes with the phagolysosomal pathway, suggesting it may limit the diversity of antigens processed and presented to T cells. We hypothesized that in the absence of IL-27 signaling, BCG vaccination induces antigen-specific T cells that recognize a greater number of antigens and provide enhanced protection during M. tuberculosis (Mtb) challenge. CD3+ T cells isolated from IL-27Rα KO mice vaccinated with BCG as neonates were more responsive to BCG and a Mtb peptide pool than T cells from vaccinated WT mice. Adoptive transfer of IL-27Rα KO T cells provided more consistent protection against Mtb than WT, but this was not observed in TCRα-/- mice. A principal component analysis suggested a more consistent multifunctional cytokine response was associated IL-27Rα KO T cells. These findings enhance our understanding of IL-27 during neonatal vaccination and development of protective immunity.
PMID:40328205 | DOI:10.1016/j.tube.2025.102641
