A A Alshevskaya1, F D Kireev1, Z A Laushkina2, J A Lopatnikova1, V S Gladkikh3, J A Sennikova4, A V Karaulov5, S V Sennikov1. 1. Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia. 2. Federal State Budgetary Institution Novosibirsk Research Institute of Tuberculosis, Ministry of Health of Russian Federation, Novosibirsk, Russia. 3. Eol Labs Ltd, Novosibirsk, Institute of Computational Mathematics and Mathematical Geophysics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia. 4. Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Novosibirsk State Medical University, Novosibirsk, Russia. 5. Federal State Autonomous Educational Institution of Higher Education I M Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia.
Abstract
BACKGROUND: Tumour necrosis factor-alpha (TNF-α) and its inhibitors are involved in both defence against tuberculosis (TB) and damage to the host by TB. Notably, the change in receptor expression on cell density is a key mechanism in regulation of the biological properties of cytokines. OBJECTIVE: To study the differences in TNF-α receptor (TNFR) expression in patients with active pulmonary tuberculosis (aPTB) in correlation with the parameters of disease severity. METHODS: TNFR1/2 levels on peripheral blood mononuclear cells (PBMCs) from 45 patients with aPTB and 150 healthy controls were analysed by flow cytometry using monoclonal antibodies and QuantiBRITE beads. Soluble TNFR1/2 and TNF-α in serum were measured using an enzyme-linked immunosorbent assay. RESULTS: TNFR1 expression in aPTB patients was increased in the main populations of immune cells. Patients who were Mycobacterium tuberculosis culture-positive on bronchoscopy had higher levels of the soluble forms of TNFR1 (sTNFR1) than M. tuberculosis-negative patients. CONCLUSION: Active TB was shown to cause activation of different immune cell types by increasing TNFR1 expression on cells and reducing sTNFR1 expression compared with healthy controls. M. tuberculosis-positive patients with disseminated infection had the highest sTNFR1 serum level compared with other patients, but did not differ in receptor expression on PBMCs.
BACKGROUND:Tumour necrosis factor-alpha (TNF-α) and its inhibitors are involved in both defence against tuberculosis (TB) and damage to the host by TB. Notably, the change in receptor expression on cell density is a key mechanism in regulation of the biological properties of cytokines. OBJECTIVE: To study the differences in TNF-α receptor (TNFR) expression in patients with active pulmonary tuberculosis (aPTB) in correlation with the parameters of disease severity. METHODS:TNFR1/2 levels on peripheral blood mononuclear cells (PBMCs) from 45 patients with aPTB and 150 healthy controls were analysed by flow cytometry using monoclonal antibodies and QuantiBRITE beads. Soluble TNFR1/2 and TNF-α in serum were measured using an enzyme-linked immunosorbent assay. RESULTS:TNFR1 expression in aPTB patients was increased in the main populations of immune cells. Patients who were Mycobacterium tuberculosis culture-positive on bronchoscopy had higher levels of the soluble forms of TNFR1 (sTNFR1) than M. tuberculosis-negative patients. CONCLUSION: Active TB was shown to cause activation of different immune cell types by increasing TNFR1 expression on cells and reducing sTNFR1 expression compared with healthy controls. M. tuberculosis-positivepatients with disseminated infection had the highest sTNFR1 serum level compared with other patients, but did not differ in receptor expression on PBMCs.
Authors: Milla R McLean; Kathleen M Wragg; Ester Lopez; Sandra A Kiazyk; Terry Blake Ball; Joe Bueti; Stephen J Kent; Jennifer A Juno; Amy W Chung Journal: Clin Transl Immunology Date: 2021-11-05