Comparative immune responses to M. tuberculosis in individuals with latent infection or sterile protection against infection

Post Date: 
2022-07-13
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Publication: 
bioRxiv
Summary: 

Summary To identify immunologic targets for tuberculosis vaccines more efficacious than BCG, we investigated the immune responses that differentiate individuals with sterile protection against M. tuberculosis (Mtb) infection (TB-resisters) from those who develop latent tuberculosis infection (LTBI-participants). TB-resisters showed higher proportions of conventional and unconventional T cells with markers of cytotoxicity, immunologic checkpoint inhibitors, and polyfunctionality in unstimulated and ex vivo Mtb-stimulated mononuclear cells. Antigen presenting cells and NK cells did not significantly differentiate TB-resisters from LTBI-participants. A complementary analysis of immune responses in BCG recipients with minimal exposure to tuberculosis by virtue of having lived most of their lives in areas of low TB endemicity revealed very different unstimulated and Mtb-stimulated immunologic profiles and lower T cell and antigen presenting cell polyfunctionality compared to both TB-resisters and LTBI-participants. A combination of increased cytotoxic and regulatory responses may contribute to protection against tuberculosis and may be targeted by new vaccines.

Citation: 
Summary To identify immunologic targets for tuberculosis vaccines more efficacious than BCG, we investigated the immune responses that differentiate individuals with sterile protection against M. tuberculosis (Mtb) infection (TB-resisters) from those who develop latent tuberculosis infection (LTBI-participants). TB-resisters showed higher proportions of conventional and unconventional T cells with markers of cytotoxicity, immunologic checkpoint inhibitors, and polyfunctionality in unstimulated and ex vivo Mtb-stimulated mononuclear cells. Antigen presenting cells and NK cells did not significantly differentiate TB-resisters from LTBI-participants. A complementary analysis of immune responses in BCG recipients with minimal exposure to tuberculosis by virtue of having lived most of their lives in areas of low TB endemicity revealed very different unstimulated and Mtb-stimulated immunologic profiles and lower T cell and antigen presenting cell polyfunctionality compared to both TB-resisters and LTBI-participants. A combination of increased cytotoxic and regulatory responses may contribute to protection against tuberculosis and may be targeted by new vaccines.