Al Leslie
Prof Al Leslie is an immunologist interested in the immunopathology of TB and HIV. His group at AHRI has a particular focus on the host-pathogen interactions that occur in tissue, particularly in the lung in the case of TB. Their work on the adaptive and innate immune response to TB, using flow and mass cytometry, histology and RNA sequencing, has revealed tissue-specific aspects of both the protective and pathogenic of TB immunity that may inform novel treatments and diagnostics. They make use of 3D-granuloma models to explore tissue-specific correlates of protective immunity and pathology, with the aim of identifying potential targets for host-directed therapies and biomarkers of disease progression. Novel potential TB biomarkers are tested in more accessible samples (blood and sputum) using well-established clinical cohorts in Durban and AHRI’s large population research platform in rural KwaZulu-Natal. Similarly, his group is interested in understanding how HIV affects the development and maintenance of immune responses in tissue. Several of their studies have shown that HIV has a much more profound effect on tissues such as the gut and secondary lymphoid organs than on the blood, which is more traditionally studied.
Get in touch with Al via al.leslie@ahri.org
Click here for a full list of publications.
Leslie Group
Prof Al Leslie’s research group at AHRI investigates the innate immune response to TB, HIV and the co-infection of these diseases, and how novel aspects of this response may potentially be exploited to improve patient outcomes. Innate immune cells are among the first to encounter invading pathogens, and the outcome of this interaction is a key factor in the subsequent course of infection. However, despite over 25 years of research in HIV and perhaps over a century for TB, there is still much about the innate immune response to both pathogens that remains unclear. This knowledge gap is partly due to the fact that aspects of the innate response are hard to study. Neutrophils, for example, which are increasingly thought to be central in the immune response to both HIV and TB, must be worked on fresh and cannot be frozen down for investigation at a later time or in a different location.
Additionally, some of the most important interactions between innate immune cells and these pathogens occur in the tissue and not in peripheral blood, which by necessity is what most HIV and TB research is based on. Through AHRI’s unique collaborations and cutting-edge laboratory facilities, Leslie Group members are able to study to fresh blood, sputum and tissue samples from individuals infected with TB, with and without HIV co-infection, allowing lab members to investigate the neutrophil response to both disease states. Using multi-colour flow cytometry, ex-vivo functional assays and transcriptomic and proteomic analysis of sorted cells, scientists are uncovering new data about how this important immune subset is altered. This has already given new insights into disease pathology and highlighted potential novel biomarkers and treatment interventions.
Meet the Team
Thabo Mpotje
Research associate
Thabo Mpotje is a research associate specialising in TB immunopathogenesis, host-directed therapies (HDTs), and post-TB lung disease. His research focuses on macrophage heterogeneity and T-cell dysfunction in TB-associated lung pathology and pulmonary fibrosis, with the aim of identifying novel therapeutic targets to improve long-term outcomes following TB.
Sibongiseni Poswayo
Postdoctoral fellow
Sibongiseni Poswayo is a postdoctoral fellow in the Leslie group, where she investigates clonal functional T-cell determinants of protection and pathogenesis in tuberculosis. She holds a PhD in clinical sciences and immunology from the University of Cape Town (UCT). Her doctoral work centred on host-directed therapies and host immune responses to intracellular bacterial infections, specifically Listeria monocytogenes and Mycobacterium tuberculosis.
Mark Chambers
Postdoctoral fellow
Mark is a postdoc in the Leslie group, currently focusing on the potential of neutrophils as a clinically useful biomarker for pulmonary and sub-clinical tuberculosis. He is also investigating the potential influence concurrent respiratory infections could have on TB disease onset. Mark completed his BSc and PhD at UKZN, where he worked on developing ligands for the Alzheimer's protein BACE1 using a combination of thermal shift assays and the zebrafish Danio Rerio model.
Mahlatse Maseeme
PhD student
Mahlatse graduated cum laude from UKZN in 2023 with a masters project that focused on the metabolic impact of TB disease - with and without HIV co-infection - on leukocytes. His PhD is focused on identifying immune correlates of protection induced by ongoing natural TB infection, identified by activated Mtb specific CD4 phenotype.
Mzabalazo Nsimbi
PhD student
Mzabalazo (Mza) holds an MSc from UKZN. He joined the Leslie group in 2022 as a lab technologist, where he assisted with processing blood samples, lung and tonsil tissue, and was also involved with the development of an organoid model from tonsil. Mza is currently pursuing a PhD in immunology, investigating the impact of sex on immune development in sex discordant twins.
Sonam Sahadeo
PhD student
Sonam Sahadeo completed her MMedSc in immunology and virology with the Leslie group at Africa Health Research Institute and the University of KwaZulu-Natal, under the supervision of Prof Al Leslie and Dr Mark Chambers. Her research characterised fibroblast-macrophage crosstalk in TB-infected human lung tissue, examining its role in granuloma progression and post-TB lung disease. She is now pursuing a PhD in immunology, continuing her work on the immunopathology of tuberculosis.
Tayla Smit
PhD Student
Tayla Smith obtained her BSc in chemistry, BSc honours in molecular biology (cum laude), and MSc in molecular biology (cum laude) from Stellenbosch University. She is currently pursuing a PhD through University College London, with her research focussed on immune dysregulation in virally suppressed HIV-TB co-infection. Her work incorporates bulk transcriptional profiling, single-cell RNA sequencing, and 3D infection models to better understand host-pathogen interactions and immune responses.
Olivette Varathan
PhD student
Olivette holds an MSc in medical virology from Stellenbosch University, where she studied HIV-1 recombinant forms circulating in South Africa. She joined the Leslie group as a research technician in 2023 and is currently a PhD student investigating immune responses across the TB disease spectrum. Using single-cell transcriptomics, her research aims to identify immune signatures and potential biomarkers to improve TB diagnosis.
Lindiwe Jhamba
Laboratory supervisor
Lindiwe holds a master of medical science (virology) from the University of KwaZulu-Natal. Her research focused on the genetic characterisation on viral blips in virally suppressed individuals on HIV antiretroviral therapy. She joined AHRI in 2022 as a research lab technician, investigating the effects of broadly neutralising antibodies in HIV. In 2024, she joined the Leslie group where she currently she serves as the laboratory supervisor.
Wilfred Sibiya
Research assistant
Wilfred Sibiya completed his master of medical science (microbiology) in the Leslie laboratory at Africa Health Research Institute (AHRI), supervised by Prof Alasdair Leslie and Dr Mark Chambers. His research used a human 3D granuloma model to investigate sex-based differences in immune responses to Mycobacterium tuberculosis and explore the underlying biological mechanisms involving hormones, immune cells, and cytokines.
Selected Recent Publications
Byrne, E. H., Anahtar, M. N., Cohen, K. E., Moodley, A., Padavattan, N., Ismail, N., Bowman, B. A., Olson, G. S., Mabhula, A., Leslie, A., Ndung'u, T., Walker, B. D., Ghebremichael, M. S., Dong, K. L., & Kwon, D. S. (2016). Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study. Lancet Infect Dis, 16(4), 441-448. doi: 10.1016/s1473-3099(15)00429-6.
Kloverpris, H. N., Kazer, S. W., Mjosberg, J., Mabuka, J. M., Wellmann, A., Ndhlovu, Z., Yadon, M. C., Nhamoyebonde, S., Muenchhoff, M., Simoni, Y., Andersson, F., Kuhn, W., Garrett, N., Burgers, W. A., Kamya, P., Pretorius, K., Dong, K., Moodley, A., Newell, E. W., Kasprowicz, V., Abdool Karim, S. S., Goulder, P., Shalek, A. K., Walker, B. D., Ndung'u, T., & Leslie, A. (2016). Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression. Immunity, 44(2), 391-405. doi: 10.1016/j.immuni.2016.01.006.
Muenchhoff, M., Adland, E., Karimanzira, O., Crowther, C., Pace, M., Csala, A., Leitman, E., Moonsamy, A., McGregor, C., Hurst, J., Groll, A., Mori, M., Sinmyee, S., Thobakgale, C., Tudor-Williams, G., Prendergast, A. J., Kloverpris, H., Roider, J., Leslie, A., Shingadia, D., Brits, T., Daniels, S., Frater, J., Willberg, C. B., Walker, B. D., Ndung'u, T., Jooste, P., Moore, P. L., Morris, L., & Goulder, P. (2016). Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection. Sci Transl Med, 8(358), 358ra125. doi: 10.1126/scitranslmed.aag1048.
Pichulik, T., Khatamzas, E., Liu, X., Brain, O., Delmiro Garcia, M., Leslie, A., Danis, B., Mayer, A., Baban, D., Ragoussis, J., Weber, A. N., & Simmons, A. (2016). Pattern recognition receptor mediated downregulation of microRNA-650 fine-tunes MxA expression in dendritic cells infected with influenza A virus. Eur J Immunol, 46(1), 167-177. doi: 10.1002/eji.201444970.
Kloverpris, H. N., Leslie, A., & Goulder, P. (2015). Role of HLA Adaptation in HIV Evolution. Front Immunol, 6, 665. doi: 10.3389/fimmu.2015.00665.