Lower IL-7 Receptor Expression of Monocytes Impairs Antimycobacterial Effector Functions in Patients with Tuberculosis
- 15 May 2021
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 206 (10), 2430-2440
- https://doi.org/10.4049/jimmunol.2001256
Abstract
Altered monocyte differentiation and effector functions characterize immune pathogenesis of tuberculosis. IL-7 is an important factor for proliferation of T cells and impaired IL-7 sensitivity due to decreased IL-7 receptor α-chain (IL-7Rα) expression was found in patients with acute tuberculosis. Peripheral blood monocytes have moderate IL-7Rα expression and increased IL-7Rα levels were described for inflammatory diseases. In this study, we investigated a potential role of IL-7 and IL-7Rα expression for monocyte functions in tuberculosis. We analyzed the phenotype of monocytes in the blood from tuberculosis patients (n = 33), asymptomatic contacts of tuberculosis patients (contacts; n = 30), and healthy controls (n = 20) from Ghana by multicolor flow cytometry. Mycobacterial components were analyzed for their capacity to induce IL-7Rα expression in monocytes. Functional effects of monocyte to IL-7 were measured during signaling and by using an antimycobacterial in vitro kill assay. Monocytes were more frequent in peripheral blood from patients with tuberculosis and especially higher proportions of CD14+/CD16+ (M1/2) monocytes with increased PD-L1 expression characterized acute tuberculosis. IL-7Rα expression was decreased particularly on M1/2 monocytes from patients with tuberculosis and aberrant low expression IL-7Rα correlated with high PD-L1 levels. Constitutive low pSTAT5 levels of monocytes ex vivo and impaired IL-7 response confirmed functionally decreased monocyte IL-7 sensitivity of patients with tuberculosis. Mycobacteria and mycobacterial cell wall components induced IL-7 receptor expression in monocytes and IL-7 boosted mycobacterial killing by monocyte-derived macrophages in vitro. We demonstrated impaired monocyte IL-7 receptor expression as well as IL-7 sensitivity in tuberculosis with potential effects on antimycobacterial effector functions.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (JA 1479/9-1)
- Jürgen Manchot Stiftung (MOI-3)
This publication has 51 references indexed in Scilit:
- IL-7 in human health and diseaseSeminars in Immunology, 2012
- Anti–IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell functionProceedings of the National Academy of Sciences of the United States of America, 2012
- IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cellsProceedings of the National Academy of Sciences of the United States of America, 2012
- Intravital Imaging Reveals Limited Antigen Presentation and T Cell Effector Function in Mycobacterial GranulomasImmunity, 2011
- Paradoxical role of CD16+CCR2+CCR5+ monocytes in tuberculosis: efficient APC in pleural effusion but also mark disease severity in bloodJournal of Leukocyte Biology, 2011
- Mycobacterium tuberculosis impairs dendritic cell response by altering CD1b, DC‐SIGN and MR profileImmunology & Cell Biology, 2010
- Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing TuberculosisClinical and Vaccine Immunology, 2008
- Interleukin-7 induced immunopathology in arthritisAnnals Of The Rheumatic Diseases, 2006
- Interleukin-7 Induces Anti-Mycobacterium avium Activity in Human Monocyte Derived MacrophagesThe Journal of Infectious Diseases, 1996
- Small (CD14+/CD16+) Monocytes and Regular Monocytes in Human BloodPathobiology, 1991