Poster Presentation CD1-MR1 2024

MAIT cell functional profiles in highly exposed healthcare workers with resistance to Mycobacterium tuberculosis infection.   (#212)

Avuyonke Mr Balfour 1 2 , Nomawethu Ms Masina 1 2 , Abulele Mr Bekiswa 1 2 , Rene Ms Goliath 2 , Katalin Dr. Wilkinson 3 4 5 , Charlotte Dr. Schutz 1 2 4 , Graeme Prof. Meintjes 1 2 4 , Muki Prof. Shey 1 2 4
  1. Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa
  2. Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa
  3. Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), ), Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa
  4. Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa
  5. The Francis Crick Institute, London, United Kingdom

Background

A small proportion of individuals can resist Mycobacterium tuberculosis (Mtb) infection despite intense environmental exposure and these people are known as ‘resisters’. Unconventional and innate-like T cells such as mucosal-associated invariant T (MAIT) cells may contribute to the initial clearance of Mtb infection due to their ability to become rapidly activated with or without antigen recognition. This study investigated the frequencies and functions of MAIT cells in resisters in comparison with individuals with latent TB infection (LTBI).

Methods

HIV uninfected healthcare workers who had worked in TB health care facilities for a minimum of 5 years were screened for Mtb sensitization using the QuantiFERON TB Gold Plus assay (QFT-Plus TB Gold) and the tuberculin skin test (TST). Participants testing negative for both tests (resisters, n = 23) and those positive for both tests (LTBI, n = 15) were enrolled and blood was collected for peripheral blood mononuclear cell (PBMC) isolation. PBMCs were stimulated with live H37Rv Mtb strain for 18 hours, and supernatants were collected for Luminex analysis. PBMCs were stimulated for a further 6 hours in the presence of Golgi inhibitors and MAIT cells were identified using MR1-tetramer, functions were assessed using flow cytometry.

Results

Frequencies of blood MAIT cells were similar between resisters and LTBI group. In response to Mtb stimulation, LTBI participants had higher frequencies of MAIT cells expressing IFN-g (p =0.048), median[IQR]: 24.01[9.09-25.80] compared to resisters, 3.48[11.10-17.96] and higher granzyme B (p=0.024), 50.60[35.60-65.66] compared to resisters 26.88[18.79-59.53]. For soluble cytokines, there was a trend of higher concentrations (pg/mL) of IFN-a (a MAIT activating cytokine) in resisters (p=0.072), 1.37[0.038-3.09] compared to LTBI: 0[0-1.88].

Conclusions

Resisters had similar frequencies of MAIT cells but lower Mtb-specific MAIT cell cytokine expression compared to LTBI. Further research is underway exploring the role of MAIT cells in resistance to tuberculosis.