Format

Send to

Choose Destination
Sci Rep. 2017 Sep 20;7(1):11948. doi: 10.1038/s41598-017-10773-5.

Circulating Mycobacterium tuberculosis DosR latency antigen-specific, polyfunctional, regulatory IL10+ Th17 CD4 T-cells differentiate latent from active tuberculosis.

Author information

1
Laboratory of Immunology of HIV-TB co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India.
2
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
3
Department of Infectious Diseases, St John's Research Institute, Bangalore, India.
4
Department of Pulmonary Medicine & Department of Infectious Diseases, St John's Research Institute, Bangalore, India.
5
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
6
Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America.
7
Laboratory of Immunology of HIV-TB co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India. anna.vyakarnam@kcl.ac.uk.
8
Dept. Infectious Diseases, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Campus, London, SE19RT, United Kingdom. anna.vyakarnam@kcl.ac.uk.

Abstract

The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB. The polyfunctionality score integrating up to 31 DosR-specific CD4 T-cell functional profiles was significantly higher in LTBI than EPTB or PTB subjects. Further analysis of 256 DosR-specific T-cell functional profiles identified regulatory IL10 + Th17 cells (IL10+IL17A+IL17F+IL22+) to be significantly enriched in LTBI; in contrast to pro-inflammatory Th17 cells (IFNγ+IL17A+/IL10-) in the blood and lung of EPTB and PTB subjects respectively. A blood polyfunctional, Mtb DosR latency antigen specific, regulatory, central memory response is therefore a novel functional component of T-cell immunity in latent TB and potential correlate of protection.

PMID:
28931830
PMCID:
PMC5607261
DOI:
10.1038/s41598-017-10773-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center