Differential expression of HLA-G and ILT-2 receptor in human tuberculosis: Localized versus disseminated disease

• Published in: Human immunology 2016-09, Vol.77 (9), p.746-753
• Main Authors: Saurabh, Abhinav, Thakral, Deepshi, Mourya, Manish K, Singh, Amar, Mohan, Anant, Bhatnagar, Anuj K, Mitra, Dipendra K, Kanga, Uma
• Format: Article
• Language: English
• Subjects: Adult; Allergy and Immunology; Antigens, CD - genetics; Antigens, CD - metabolism; Biomarkers - metabolism; Cells, Cultured; Diagnosis, Differential; Disease Progression; Female; HLA-G; HLA-G Antigens - genetics; HLA-G Antigens - metabolism; Humans; ILT-2; Leukocyte Immunoglobulin-like Receptor B1; Male; Miliary tuberculosis; Monocytes - immunology; Monocytes - metabolism; Mycobacterium; Mycobacterium - physiology; Pleural Effusion - diagnosis; Pleural Effusion - genetics; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transcriptome; Tuberculosis, Miliary - diagnosis; Tuberculosis, Miliary - genetics; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - genetics; Tuberculosis-pleural effusion; Young Adult
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2016.01.004

Abstract Human leukocyte antigen-G (HLA-G) is an anti-inflammatory and immunosuppressive molecule that can modulate immune cell activation. The role of HLA-G in tuberculosis, an immune-mediated and chronic bacterial disease remains to be elucidated. We investigated the expression profile of soluble and membrane bound HLA-G in pulmonary TB (PTB), TB pleural effusion (TB-PE, localized disease) and Miliary TB (disseminated form). The expression of HLA-G receptor, ILT-2 was also determined on the immune cells. We observed that the plasma sHLA-G levels were significantly increased in Miliary TB than in TB-PE patients. In contrast, immunophenotyping revealed that the percent frequency of CD3+ T cells expressing HLA-G was significantly reduced in Miliary TB as compared to TB-PE, whereas frequency of CD14+ monocytes expressing HLA-G was significantly higher in TB-PE patients. Strikingly in the TB-PE cases, comparison of disease site, i.e. pleural effusion with peripheral blood showed increased expression of both soluble and surface HLA-G, whereas ILT-2 expressing cells were reduced at the local disease site. Furthermore, we demonstrated that in TB-PE cases, HLA-G expression on CD3+ T cells was influenced by broad spectrum MMP inhibitor. Thus, differential expression of HLA-G could potentially be a useful biomarker to distinguish different states of TB disease.