PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease

Frontiers in Immunology

卷:12

Federica De Santis¹  Maurizio Fraziano¹  Alessandra Romagnoli²  Rita Casetti³  Chiara Agrati³  Veronica Bordoni³  Stefania Notari³  Germana Grassi³  Eleonora Cimini³  Alessandra Sacchi³  Delia Goletti⁴  Alessandra Aiello⁴  Gilda Cuzzi⁴  Gina Gualano⁵  Fabrizio Palmieri⁵  Silvia Mosti⁵  Valentina Vanini⁶ 

[1] Department of Biology, University of Rome “Tor Vergata”, Rome, Italy;

[2] Department of Epidemiology, Preclinical Research, and Advanced Diagnostics, National Institute for Infectious Diseases ‘Lazzaro Spallanzani’-IRCCS, Rome, Italy;

[3] Laboratory of Cellular Immunology and Pharmacology, National Institute for infectious Diseases “Lazzaro Spallanzani”-IRCCS, Rome, Italy;

[4] Laboratory of Translational Research, National Institute for infectious Diseases “Lazzaro Spallanzani”-IRCCS, Rome, Italy;

[5] Respiratory Infectious Diseases Unit, National Institute for infectious Diseases “Lazzaro Spallanzani”-IRCCS, Rome, Italy;

[6] UOS Professioni Sanitarie Tecniche National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy;

关键词: MDSC (myeloid-derived suppressor cell);    tuberculosis;    LTBI (latent TB infections);    active TB;    monocytes;   

DOI  :  10.3389/fimmu.2021.594376

来源: DOAJ

【 摘 要 】

Tuberculosis (TB), due to Mycobacterium tuberculosis infection, is still the principal cause of death caused by a single infectious agent. The balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. Factors defining this variety are unclear and likely involve both mycobacterial and immunological components. Myeloid derived suppressor cells (MDSC) have been shown to be expanded during TB, but their role in human TB pathogenesis is not clear. We evaluated the frequency of circulating MDSC by flow-cytometry in 19 patients with active TB, 18 with latent TB infection (LTBI), and 12 healthy donors (HD) as control. Moreover, we investigated the capacity of MDSC to modulate the mycobactericidal activity of monocytes. The association between MDSC level and TB chest X-ray severity score was analyzed. We observed that, unlike active TB, polymorphonuclear (PMN)-MDSC are not expanded in LTBI patients, and, by performing a receiver operating characteristic (ROC) curve analysis, we found that PMN-MDSC frequency supported the discrimination between active disease and LTBI. Interestingly, we observed an association between PMN-MDSC levels and the severity of TB disease evaluated by chest X-ray. Specifically, PMN-MDSC frequency was higher in those classified with a low/mild severity score compared to those classified with a high severity score. Moreover, PMN-MDSC can impact mycobacterial growth by inducing ROS production in Bacillus Calmette et Guerin (BCG)-infected monocytes. This effect was lost when tested with M. tuberculosis (MTB), In conclusion, our data indicate that the elevated frequency of PMN-MDSC in IGRA-positive individuals is associated with active TB. Our findings also pointed out a beneficial role of PMN-MDSC during human active TB, most likely associated with the limitation of inflammation-induced tissue damage.

【 授权许可】

Unknown