Mycobacteria-induced immune responses by mucosal-associated invariant T (MAIT) cells are impaired in patients with tuberculosis (TB) and HIV-associated TB
A Balfour1, C Schutz1, R Goliath1, KA Wilkinson1,2, G Meintjes1, M Shey1
1Wellcome Centre for Infectious Diseases Research in Africa & Department of Medicine, University of Cape Town, Cape Town, South Africa; 2The Francis Crick Institute, London, United Kingdom
Background and objectives: MAIT cells are non-classical T lymphocytes that recognize and rapidly respond to microbial vitamin B metabolites and have the capacity to kill bacteria-infected cells. Circulating MAIT cell numbers decrease in patients with active TB and HIV, but previous findings regarding functional changes have been conflicting. We conducted a cross sectional study to assess the effect of HIV, TB and HIV-associated TB (HIV–TB) on MAIT cell numbers, activation, inhibitory and functional profile in a TB endemic setting in South Africa.
Methods: Blood was collected from healthy controls (HC; n=26), individuals with HIV infection only (HIV; n=30), with active TB only (aTB; n=30) and with HIV–TB (n=26). All TB participants were newly diagnosed with TB and sampled prior to treatment. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with BCG expressing GFP (BCG-GFP) or heat-killed (HK) Mycobacterium tuberculosis (Mtb) and analysed using flow cytometry.
Results: There were lower frequencies of MAIT cells in HIV (median: 0.3%; P=0.04) and aTB (0.4%; P=0.02) compared with HC (0.7%). BCG-specific MAIT cell activation (measured by HLA-DR expression [median fluorescent intensity]) was higher in aTB (230; P=0.006) and HIV–TB (280; P=0.0008) compared with HC (114). BCG-induced MAIT cell degranulation (measured by CD107a expression) was lower in aTB (4.5%; P=0.003) and HIV–TB (4.6%; P=0.04) compared with HC (9.8%). Similarly, IFN-γ expression was lower in aTB and HIV–TB (3.2% and 1.0%; P=0.0005 and P=0.0006, respectively) compared with HC (17.6%). Similar results to BCG were obtained with HK-Mtb stimulation. Compared with HC, MAIT cells from individuals with aTB had higher basal PD-1 expression (2.1% versus 5.2%; P<0.0001). See Figure 1.
(Abstract P52)
Conclusions: Our data show that compared with HC, HIV and aTB result in a decrease in circulating MAIT cells, while aTB and HIV–TB resulted in a significant increase in activation and inhibitory status, and an impaired mycobacteria-induced functional profile.
Funding: This study was funded by the National Research Foundation (NRF) of South Africa and the Wellcome Trust.
