Mucosal-associated invariant T cells from patients with tuberculosis exhibit impaired immune response

Objectives: To identify factors which regulate MAIT cell response to Mycobacterium tuberculosis antigens, and to investigate the role of MAIT cells in patients with active tuberculosis. Methods: Immune response of MAIT cells to M. tuberculosis antigens were compared between patients with active TB and healthy controls by flow cytometry and RNA sequencing. Results: IFN-gamma response of MAIT cells to M. tuberculosis lysates was dramatically improved by signal 3 cytokine IL-15 (p = 0.0002). Patients with active TB exhibited highly reduced IFN-gamma production in MAIT cells stimulated with M. tuberculosis lysates/IL-15 compared with healthy controls (p < 0.0001) and individuals with latent TB infection (p = 0.0008). RNA sequencing of flow-sorted MAIT cells from patients with TB and healthy controls identified numerous differentially expressed genes, and the expression of genes that encode IFN-gamma, TNF-alpha, IL-17F, granulysin and granzyme B were all down-regulated in patients with TB. MAIT cells from patients with TB has significantly lower expression of gamma c receptor than those from healthy controls under condition of Mtb lysates/IL-15 stimulation (p = 0.0028). Blockade of both gc and IL-2R beta receptors resulted in highly reduced frequency of IFN-gamma-producing MAIT cells (79.4%) (p = 0.0011). Conclusions: MAIT cells from patients with active TB exhibited impaired cytokine and cytotoxic response to M. tuberculosis antigens. (C) 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.