| Autor: |
Ogongo P; Africa Health Research Institute, Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya., Tezera LB; National Institute for Health Research Southampton Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, and.; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.; Division of Infection and Immunity, University College London, London, United Kingdom., Ardain A; Africa Health Research Institute, Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa., Nhamoyebonde S; Africa Health Research Institute, Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa., Ramsuran D; Africa Health Research Institute, Durban, South Africa., Singh A; Africa Health Research Institute, Durban, South Africa., Ng'oepe A; Africa Health Research Institute, Durban, South Africa., Karim F; Africa Health Research Institute, Durban, South Africa., Naidoo T; Africa Health Research Institute, Durban, South Africa., Khan K; Africa Health Research Institute, Durban, South Africa., Dullabh KJ; Department of Cardiothoracic Surgery, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Fehlings M; ImmunoScape Pte Ltd, Singapore, Singapore., Lee BH; ImmunoScape Pte Ltd, Singapore, Singapore., Nardin A; ImmunoScape Pte Ltd, Singapore, Singapore., Lindestam Arlehamn CS; La Jolla Institute for Immunology, La Jolla, California, USA., Sette A; La Jolla Institute for Immunology, La Jolla, California, USA.; Department of Medicine, University of California, San Diego, La Jolla, California, USA., Behar SM; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Steyn AJ; Africa Health Research Institute, Durban, South Africa.; Department of Microbiology and.; Center for AIDS Research and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA., Madansein R; Department of Cardiothoracic Surgery, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Kløverpris HN; Africa Health Research Institute, Durban, South Africa.; Division of Infection and Immunity, University College London, London, United Kingdom.; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Elkington PT; National Institute for Health Research Southampton Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, and.; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom., Leslie A; Africa Health Research Institute, Durban, South Africa.; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.; Division of Infection and Immunity, University College London, London, United Kingdom. |
| Abstrakt: |
T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation. Using freshly resected lung tissue, from individuals with active or previous TB, we identified distinct CD4+ and CD8+ Trm-like clusters within TB-diseased lung tissue that were functional and enriched for IL-17-producing cells. M. tuberculosis-specific CD4+ T cells producing TNF-α, IL-2, and IL-17 were highly expanded in the lung compared with matched blood samples, in which IL-17+ cells were largely absent. Strikingly, the frequency of M. tuberculosis-specific lung T cells making IL-17, but not other cytokines, inversely correlated with the plasma IL-1β levels, suggesting a potential link with disease severity. Using a human granuloma model, we showed the addition of either exogenous IL-17 or IL-2 enhanced immune control of M. tuberculosis and was associated with increased NO production. Taken together, these data support an important role for M. tuberculosis-specific Trm-like, IL-17-producing cells in the immune control of M. tuberculosis in the human lung. |
