Cytokine-induced transient monocyte IL-7Ra expression and the serum milieu in tuberculosis

Bacterial components and cytokines induce IL-7 receptor (IL-7R alpha) expression in monocytes. Aberrant low IL-7R alpha expression of monocytes has been identified as a feature of tuberculosis immunopathology. Here, we investigated the mechanisms underlying IL-7R alpha regulation of monocytes and tuberculosis serum effects on IL-7R alpha expression. Serum samples from tuberculosis patients and healthy controls, cytokine candidates, and mycobacterial components were analyzed for in vitro effects on IL-7R alpha expression of primary monocytes, monocyte-derived macrophages (MDM), and monocyte cell lines. IL-7R alpha regulation during culture and the role of FoxO1 were characterized. In vitro activation-induced IL-7R alpha expression in human monocytes and serum samples from tuberculosis patients boosted IL-7R alpha expression. Although pathognomonic tuberculosis cytokines were not associated with serum effects, we identified cytokines (i.e., GM-CSF, IL-1 beta, TNF-alpha, IFN-gamma) that induced IL-7R alpha expression in monocytes and/or MDM comparable to mycobacterial components. Blocking of cytokine subsets (i.e., IL-1 beta/TNF-alpha in monocytes, GM-CSF in MDM) largely diminished IL-7R alpha expression induced by mycobacterial components. Finally, we showed that in vitro-induced IL-7R alpha expression was transient and dependent on constitutive FoxO1 expression in primary monocytes and monocyte cell lines. This study demonstrated the crucial roles of cytokines and constitutive FoxO1 expression for transient IL-7R alpha expression in monocytes.