Tuberculosis antigen‐induced expression of IFN‐α in tuberculosis patients inhibits production of IL‐1β

Abstract

The mechanism by which IFN-α regulates the host response to Mycobacterium tuberculosis (M.tb) infection in humans is poorly understood. In the present study, we found that freshly isolated pleural fluid mononuclear cells (PFMCs) from tuberculous pleural effusion but not peripheral blood mononuclear cells (PBMCs) spontaneously expressed IFN-α and IL-1β in vivo. In addition, exogenous IFN-α significantly inhibited production of IL-1β in PFMCs after stimulation with Bacillus Calmette-Guérin (BCG). To further evaluate the effect of endogenous IFN-α on BCG-induced IL-1β production, a neutralizing antibody to IFN-α was added to the cultures of BCG-stimulated PFMCs. As expected, neutralization of IFN-α by antibody significantly enhanced the production of IL-1β. Notably, we showed that IFN-α inhibited production of IL-1β through 2 distinct mechanisms: IFN-α signaling, via the STAT1 transcription factor, suppressed caspase-1-dependent IL-1β maturation, and IFN-α induced the production of IL-10 in a STAT1-dependent manner in which IL-10 reduced the abundance of IL-1β. In contrast, we found that IFN-α enhanced the production of IFN-γ, and IFN-γ also suppressed IL-1β production in the PFMCs during BCG stimulation. Our findings demonstrate that IFN-α employs distinct pathways for regulating IL-1β production and reveal that in the case of M.tb infection, the induction of IFN-α and IFN-γ might be associated with M.tb immune escape and disease progression in infected humans.-Ma, J., Yang, B., Yu, S., Zhang, Y., Zhang, X., Lao, S., Chen, X., Li, B., Wu, C. Tuberculosis antigen-induced expression of IFN-α in tuberculosis patients inhibits production of IL-1β.

Interferon‐α curbs production of interleukin‐22 by human peripheral blood mononuclear cells exposed to live Borrelia burgdorferi

“…The present observation of IFN-α modulating production of IL-1β concurs with previous reports demonstrating, albeit in other experimental systems, reduced pro-IL-1β expression and/or maturation under the influence of type I IFN 20,21. Specifically, type I IFN increases murine susceptibility to Candida albicans by inhibiting IL-1β biological activity 20.…”

The investigation of immunomodulatory activities of Gloeostereum�incaratum polysaccharides in cyclophosphamide-induced immunosuppression mice

“…IL-6 promotes the expression of IL-2 in T cells, which further interacts with IL-3 to promote the differentiation of T cells (36). Moreover, Th1 cells secretes IFN-α and IFN-γ, which promotes cytotoxic lymphocytes formation and activity of macrophage (37,38). IFN-γ, an essential cytokine for host defense against pathogens, can stimulate macrophages to eliminate bacterial and tumor cell, activate neutrophil and natural killer (NK) cell (37).…”

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion

“…Notably, the expression levels of PD-L1 on CD14 + monocytes increased when the PBMCs were supplemented with TPE; however, the proliferation rate remained lower than is achieved with commercial IFN-γ stimulation (16). It is possible that IFN-γ is not the only cytokine with a role in the TB microenvironment, other cytokines, such as IFN-α, may also have an effect (26,36). In a previous study it was reported that IFN-α and IFN-β strongly inhibited IFN-γ responsiveness and the production of type I cytokines (15); however, no differences in IFN-α levels were detected in the TPE, MPE and n-TB n-M groups in the present study.…”