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-γ 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-γ 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-γ, TNF-α, 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 γc receptor than those from healthy controls under condition of Mtb lysates/IL-15 stimulation (p = 0.0028). Blockade of both γc and IL-2Rβ receptors resulted in highly reduced frequency of IFN-γ-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.
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| http://dx.doi.org/10.1016/j.jinf.2015.11.010 | DOI Listing |
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