Tissue-infiltrating mucosal-associated invariant T cells play an important role against Mycobacterium tuberculosis infection in tuberculosis pleurisy.

Control of infection with Mycobacterium tuberculosis (M.tb) requires effective antigen-specific immune response, including CD4+ and CD8+ T-cell responses; however, the local immune response of mucosal-associated invariant T (MAIT) cells at the site of infection is unclear. MAIT cells are a prevalent and unique, innate T-cell population that expresses the semi-invariant T-cell receptor TCRVα7.2. Our direct ex vivo analysis demonstrates that the frequency of MAIT cells in pleural fluid was much higher than that in peripheral blood from healthy donors, but much lower than that in peripheral blood from patients with tuberculosis. M.tb-reactive MAIT cells highly expressed tissue-specific chemokine receptors (CXCR3hiCXCR4hiCCR5hiCXCR6hi) and displayed an effector memory T-cell phenotype (CD45RO+CCR7-CD62L-), which indicates preferential homing to mucosal-associated lymphoid tissues. Furthermore, the majority of MAIT cells in pleurisy fluid express tissue-resident makers (CD69+) that were only marginally present on MAIT cells from normal peripheral blood mononuclear cells. In addition, MAIT cells produce cytokines IFN-γ and TNF-α and exhibit cytotoxic activity molecules, CD107a/b and granzyme B, in response to tuberculosis-specific antigens, which suggests that MAIT cells played a significant role in immune response to M.tb in local lesions. Here, we address the potential roles for M.tb-reactive MAIT cells at the site of tuberculosis infection.-Li, J., Yu, S., Zhang, Y., Shen, J., Lao, S., Li, B., Yang, B., Wu, C. Tissue-infiltrating mucosal-associated invariant T cells play an important role against Mycobacterium tuberculosis infection in tuberculosis pleurisy.

Tuberculosis antigen-induced expression of IFN-α in tuberculosis patients inhibits production of IL-1ß.

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-1ß in vivo. In addition, exogenous IFN-α significantly inhibited production of IL-1ß in PFMCs after stimulation with Bacillus Calmette-Guérin (BCG). To further evaluate the effect of endogenous IFN-α on BCG-induced IL-1ß 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-1ß. Notably, we showed that IFN-α inhibited production of IL-1ß through 2 distinct mechanisms: IFN-α signaling, via the STAT1 transcription factor, suppressed caspase-1-dependent IL-1ß maturation, and IFN-α induced the production of IL-10 in a STAT1-dependent manner in which IL-10 reduced the abundance of IL-1ß. In contrast, we found that IFN-α enhanced the production of IFN-γ, and IFN-γ also suppressed IL-1ß production in the PFMCs during BCG stimulation. Our findings demonstrate that IFN-α employs distinct pathways for regulating IL-1ß 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-1ß.