Circulating Mycobacterium tuberculosis DosR latency antigen-specific, polyfunctional, regulatory IL10(+) Th17 CD4 T-cells differentiate latent from active tuberculosis
| Autor: | Greg Finak, Chirag Dhar, Pravat Nalini Sahoo, Annapurna Vyakarnam, Srabanti Rakshit, J Anto Jesuraj Uk, Prabhat K. Sharma, George D. Souza, Krista E. van Meijgaarden, Soumya Nayak, Vasista Adiga, Tom H. M. Ottenhoff, Stephen C. De Rosa |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Tuberculosis T cell lcsh:Medicine chemical and pharmacologic phenomena Biochemistry Mycobacterium tuberculosis Interleukin 22 03 medical and health sciences 0302 clinical medicine Tuberculosis diagnosis Antigen Immunity medicine lcsh:Science Multidisciplinary biology lcsh:R biology.organism_classification medicine.disease bacterial infections and mycoses Virology 3. Good health Interleukin 10 030104 developmental biology medicine.anatomical_structure Immunology lcsh:Q 030215 immunology |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) Scientific Reports, 7 Rakshit, S, Adiga, V, Nayak, S, Sahoo, P N, Sharma, P K, Van Meijgaarden, K E, Uk J., A J, Dhar, C, Souza, G D, Finak, G, De Rosa, S C, Ottenhoff, T H M & Vyakarnam, A 2017, ' Circulating Mycobacterium tuberculosis DosR latency antigen-specific, polyfunctional, regulatory IL10+ Th17 CD4 T-cells differentiate latent from active tuberculosis ', Scientific Reports, vol. 7, no. 1, 11948 . https://doi.org/10.1038/s41598-017-10773-5 |
| DOI: | 10.1038/s41598-017-10773-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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