Comparative immune responses to Mycobacterium tuberculosis in people with latent infection or sterilizing protection
Emilie Jalbert,
Cuining Liu,
Vidya Mave,
Nancy Lang,
Anju Kagal,
Chhaya Valvi,
Mandar Paradkar,
Nikhil Gupte,
Rahul Lokhande,
Renu Bharadwaj,
Vandana Kulkarni,
Amita Gupta,
Adriana Weinberg
Affiliations
Emilie Jalbert
Department of Pediatrics, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, USA
Cuining Liu
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, USA
Vidya Mave
Byramjee Jeejeebhoy Government Medical College- Johns Hopkins University Clinical Research Site (BJGMC-JHU CRS), Pune, Maharashtra, India; Johns Hopkins Center for Infectious Diseases in India, Pune, Maharashtra, India; School of Medicine, Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA
Nancy Lang
Department of Pediatrics, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, USA
Anju Kagal
Department of Microbiology, Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospital, Pune, Maharashtra, India
Chhaya Valvi
Department of Pediatrics, Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospital, Pune, Maharashtra, India
Mandar Paradkar
Byramjee Jeejeebhoy Government Medical College- Johns Hopkins University Clinical Research Site (BJGMC-JHU CRS), Pune, Maharashtra, India; Johns Hopkins Center for Infectious Diseases in India, Pune, Maharashtra, India; School of Medicine, Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA
Nikhil Gupte
Byramjee Jeejeebhoy Government Medical College- Johns Hopkins University Clinical Research Site (BJGMC-JHU CRS), Pune, Maharashtra, India; Johns Hopkins Center for Infectious Diseases in India, Pune, Maharashtra, India; School of Medicine, Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA
Rahul Lokhande
Department of Pulmonary Medicine, Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospital, Pune, Maharashtra, India
Renu Bharadwaj
Department of Microbiology, Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospital, Pune, Maharashtra, India
Vandana Kulkarni
Byramjee Jeejeebhoy Government Medical College- Johns Hopkins University Clinical Research Site (BJGMC-JHU CRS), Pune, Maharashtra, India; Johns Hopkins Center for Infectious Diseases in India, Pune, Maharashtra, India; School of Medicine, Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA
Amita Gupta
Johns Hopkins Center for Infectious Diseases in India, Pune, Maharashtra, India; School of Medicine, Center for Clinical Global Health Education (CCGHE), Johns Hopkins University, Baltimore, MD, USA
Adriana Weinberg
Departments of Pediatrics, Medicine and Pathology, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, USA; Corresponding author
Summary: There is great need for vaccines against tuberculosis (TB) more efficacious than the licensed BCG. Our goal was to identify new vaccine benchmarks by identifying immune responses that distinguish individuals able to eradicate the infection (TB-resisters) from individuals with latent infection (LTBI-participants). TB-resisters had higher frequencies of circulating CD8+ glucose monomycolate (GMM)+ Granzyme-B+ T cells than LTBI-participants and higher proportions of polyfunctional conventional and nonconventional T cells expressing Granzyme-B and/or PD-1 after ex vivo M. tuberculosis stimulation of blood mononuclear cells. LTBI-participants had higher expression of activation markers and cytokines, including IL10, and IFNγ. An exploratory analysis of BCG-recipients with minimal exposure to TB showed absence of CD8+GMM+Granzyme-B+ T cells, lower or equal proportions of Granzyme-B+PD-1+ polyfunctional T cells than TB-resisters and higher or equal than LTBI-participants. In conclusion, high Granzyme-B+PD-1+ T cell responses to M. tuberculosis and, possibly, of CD8+GMM+Granzyme-B+ T cells may be desirable for new TB vaccines.
