Research from two new Africa Health Research Institute (AHRI) PhD graduates sheds light on the body’s immune response to tuberculosis (TB) and gives possible clues to more effective vaccines and diagnostics.

Dr Sharon Khuzwayo and Dr Tafara Kunota recently completed their PhDs under the supervision of AHRI Faculty members Dr Emily Wong and Professor Adrie Steyn.

Dr Khuzayo’s PhD research, which was co-supervised by Professor Thumbi Ndung’u, focused on characterising the responses of a group of cells known as mucosal-associated invariant T (MAIT) cells in HIV-negative and HIV-positive individuals who had latent TB infection. She discovered that MAIT cells from the surface of the lung have previously undescribed features and that while HIV decreases MAIT cell numbers from both the circulation and the lung, it seems to preserve the different types of MAIT cells in the lung.

“TB is responsible for nearly a third of deaths in HIV infected individuals. It is important for us to understand why HIV infected people are more susceptible to respiratory infections, like TB, so we can find improved strategies to prevent such infections in these individuals,” she explained.

“Sharon’s work has shed new light on the nature of the lung’s mucosal surface as a unique immunologic niche. Sharon used a variety of technically challenging approaches – like T cell cloning and single-cell transcriptomics – to try to understand the surprising heterogeneity of MAIT cells from the bronchoalveolar space. She identified a novel subset of lung mucosal MAIT cells that appear to have tissue repair properties. Interestingly these are preserved even in people with HIV infection. I am very proud of her and all the hard work she put into this project. Sharon will always be very special to me because she is my first PhD student to graduate!” said Dr Wong.

Dr Kunota’s PhD research focused on understanding one of the mechanisms that Mycobacterium tuberculosis (Mtb) – the bacterium which causes tuberculosis – uses to counteract TB drugs. Along with his colleagues their findings conclusively demonstrated, for the first time, that Mtb is an avid producer of a gas called hydrogen sulfide (H2S).  The project went on to show that this H2S modulates processes that govern Mtb respiration, central metabolism, oxidative stress, and ultimately susceptibility to the anti-TB drug, clofazimine.

“The findings represent a significant conceptual advance that will broadly impact the TB field as H2S is a previously overlooked confounding factor in most experiments. What we have uncovered in this work represents a paradigm for how Mtb H2S metabolism promotes disease and is expected to make a vital contribution to our understanding of Mtb physiology. Once these mechanisms are known, we strongly anticipate that targeted pharmacological manipulation or new diagnostics will be developed and will result in novel approaches to TB treatment,” said Dr Kunota.

“Tafara has done some impressive work in this project and I am extremely proud of him. We are of the view that the findings will be of immediate interest to the wider scientific community, especially those with interests in Mtb physiology, bioenergetics, gasotransmitters, anti-TB drug studies, and bacterial pathogenesis,” said Professor Steyn.

Both graduates will continue their research journeys, and say they hope that these projects and their future work in science result in breakthroughs in the TB field.

“Although I may not be certain of what the future holds for me, this past year we’ve been reminded of the importance of clinical research in developing safe, effective vaccines. So, I would like some aspect of my future to be involved in clinical research that is aimed at improving the current tools we have against TB and HIV,” said Dr Khuzwayo.

“The journey continues in the research and diagnostic space, where I plan to continue leveraging my scientific experience in teams that seek practical innovative African solutions to various societal problems,” said Dr Kunota.