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Mucosal-associated invariant T cells from patients with tuberculosis exhibit impaired immune response
Jing Jiang1, Bingfen Yang1, Hongjuan An1
1Key Laboratory of Tuberculosis Prevention and Treatment, and Beijing Key Laboratory of New Techniques for Tuberculosis Diagnosis and Treatment, Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
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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