Background: MAIT cells are MR1-restricted and IL-12+IL-18 responsive¹ innate-like lymphocytes found at mucosal sites including the lungs. Human MAIT cells can be directly activated by M. tuberculosis in an MR1-dependent fashion, whilst murine MAIT cells control M. bovis BCG in an IL-12 dependent, MR1-independent manner². This project set out to assess the cytokine-mediated activation of human MAIT cells by Mtb, their ability to restrict intracellular Mtb in vitro, and their presence within the lung-associated lymph nodes of TB patients.

Methods: CD8⁺ T cells were cocultured with Mtb (H37Rv) infected THP1 cells, and blocking antibodies against MR1, or IL-12 + IL-18 were added. IFNγ, TNFα and CD107a expression were evaluated by flow cytometry. For Mtb growth-restriction, PMA-activated THP1s were infected with Mtb, washed, and cocultured with FACS sorted MAIT cells. Intracellular bacilli were released from the cells and viable colonies enumerated. To assess MAIT cell presence at the site of disease, ultrasound-guided endobronchial (EBUS) sampling was used to obtain fine-needle aspirates from the mediastinal lymph nodes of TB and control patient groups, and analysis was conducted in parallel with matched PBMCs.

Conclusions: Mtb infected THP1s robustly activated MAIT cells, and blocking MR1 had little effect on IFNγ secreted after 20h coculture, which was largely dependent on IL-12 and IL-18. FACS sorted MAIT cells reduced Mtb viability in vitro, and activated MAIT cells were observed at a higher level within the lymph nodes of TB patients, relative to control patient groups. Together, these results suggest an important cytokine-mediated anti-mycobacterial role for MAIT cells. Their presence within the lymph nodes of TB patients, and the ability of primary human MAIT cells to restrict Mtb in vitro adds further credence to the premise that MAIT cells play a protective role during tuberculosis.