Lower IL-7 Receptor Expression of Monocytes Impairs Antimycobacterial Effector Functions in Patients with Tuberculosis

• Published in: The Journal of immunology (1950) 2021-05, Vol.206 (10), p.2430-2440
• Main Authors: Adankwah, Ernest, Harelimana, Jean De Dieu, Minadzi, Difery, Aniagyei, Wilfred, Abass, Mohammed K, Batsa Debrah, Linda, Owusu, Dorcas O, Mayatepek, Ertan, Phillips, Richard O, Jacobsen, Marc
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Asymptomatic Diseases; Case-Control Studies; Child; Cohort Studies; Female; Humans; Interleukin-7 - metabolism; Macrophages - immunology; Male; Middle Aged; Monocytes - immunology; Mycobacterium tuberculosis - immunology; Receptors, Interleukin-7 - metabolism; Signal Transduction - immunology; Tuberculosis - blood; Tuberculosis - immunology; Tuberculosis - microbiology; Young Adult
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2001256

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 ( = 33), asymptomatic contacts of tuberculosis patients (contacts; = 30), and healthy controls ( = 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.