Secretion of IFN-γ Associated with Galectin-9 Production by Pleural Fluid Cells from a Patient with Extrapulmonary Tuberculosis

Abstract

In this study, we investigated the role of a matricellular protein galectin-9 (Gal-9) in pleural effusion related to tuberculosis (TB). Plasma and pleural fluid of a patient with extrapulmonary TB were analyzed for cytokine content by ELISA and Luminex. Peripheral blood mononuclear cells (PBMCs) and pleural fluid cells (PFCs) were examined for interferon-γ (IFN-γ) secretion by the enzyme-linked immunospot (ELISPOT) assay or IFN-γ ELISA, for apoptosis and necrosis by Cell Death Detection ELISA, and also underwent cell sorting. The results indicate that compared to plasma, pleural fluid had increased levels of IFN-γ (1.6 vs. 55.5 pg/mL), IL-10, IL-12p40, vascular endothelial growth factor (VEGF), and Gal-9 (3.0 vs. 936.0 pg/mL), respectively. PFCs culture supernatant exhibited higher concentration of Gal-9 compared to PBMCs in culture, consistent with enriched Gal-9 staining in the granuloma that is in closer vicinity to PFCs compared to PBMCs. PFCS displayed higher IFN-γ secretion after stimulation with TB antigens ESAT-6/CFP-10. Furthermore, in PFCs, Gal-9 alone could stimulate IFN-γ synthesis in culture or ELISPOT, which was inhibited by a Gal-9 antagonist lactose, and which may promote apoptosis and necrosis. These findings suggest that Gal-9 could modulate immune responses and participate in immunopathology of pleural effusion during TB.

Mycobacterium tuberculosis Reactivates HIV-1 via Exosome-Mediated Resetting of Cellular Redox Potential and Bioenergetics

“…Hsp90 is abundantly present in the serum of HIV-M. tuberculosis-coinfected patients (81). Galectins such as Gal3 secrete into exosomes (82) and promote redox imbalance (83), whereas Gal9 is frequently found in the plasma of TB patients (84) and reactivates HIV-1 (71). While we have characterized the proteome of M. tuberculosis exosomes derived from macrophages, it is certain that the presence of immunomodulatory proteins, lipids, and RNA of M. tuberculosis also influences HIV-1 reactivation.…”

Rapid Decline of IFN-γ Spot-Forming Cells in Pleural Lymphocytes during Treatment in a Patient with Suspected Tuberculosis Pleurisy

“…We previously reported that the level of galectin-9 (Gal-9), an apoptosis-inducing factor, is elevated in TPE, and that treatment of pleural lymphocytes with Gal-9 without antigen stimulation resulted in IFN-γ production, accompanied by apoptosis [14]. Thus, Gal-9 levels might have increased in this patient before therapy and may have decreased after therapy.…”

Galectin-9 expression correlates with efficacy of tacrolimus therapy in rheumatoid arthritis

“…Gal-9 is also expressed in vascular endothelial cells with several functions, including modulating the phosphorylation of VEGF-receptor3 and insulin-like growth factor 1, regulating the RTK pathway, mediating the adhesion between tumoral and endothelial cells, regulating the proliferation and metastasis of tumor cells [31,32]. Rodriguez-Carrio J et al reported reduced numbers of angiogenic T cells and endothelial progenitor cells in RA patients [33], but another study found an elevated percentage of circulating angiogenic T cells that positively correlated with the percentage of endothelial progenitor cells in RA patients, which regulated VEGF levels through Akt signaling with CD147 [34].…”