Abstract
Elevated matricellular proteins (MCPs), including osteopontin (OPN) and galectin-9 (Gal-9), were observed in the plasma of patients with Manila-type tuberculosis (TB) previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44) by enzyme-linked immunosorbent assay (ELISA), and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI), and 19 healthy controls (HCs) from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs). Spoligotyping showed that 20 out of 36 Mycobacterium tuberculosis (MTB) strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively) than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology.
Highlights
In 2000, Bornstein et al proposed that there is a family of secreted extracellular matrix (ECM) proteins termed “matricellular” proteins to highlight their influence on cell-matrix interactions [1]
All healthy controls (HCs) tested negative for T-SPOT.TB, and all TB patients tested positive for T-SPOT.TB
The results showed high levels of Interferon γ (IFN-γ), IL-8, inducible protein-10 (IP-10), and tumor necrosis factor α (TNF-α) in the TB group compared to HCs (Table 2)
Summary
In 2000, Bornstein et al proposed that there is a family of secreted extracellular matrix (ECM) proteins termed “matricellular” proteins to highlight their influence on cell-matrix interactions [1]. Based on this definition, several proteins have been identified as matricellular proteins (MCPs), including connective-tissue growth factors, galectins [2] and osteopontin (OPN) [3]. The intact form of OPN, reported as full-length OPN (FL-OPN), is involved in the complex pathways of coagulation and fibrinolysis, where multiple sites of FL-OPN serve as a thrombin-cleaved target During this process, the OPN fragments are produced. Elevation of trOPN levels has been reported in the recovery phase of dengue virus infection [10]
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