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.

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Al Leslie

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

Zach Porterfield  - Leslie Group

Zach Porterfield

Research collaborator

Zach is a physician-scientist focused on understanding HIV-induced changes to immunity at the level of lymph tissue – the factories that develop and refine antibodies. He is a PhD trained virologist and completed his Infectious Disease fellowship at Yale University. He holds a position at UKZN as a senior lecturer where he has a keen interest in research capacity building.

Robert Krause  - Leslie Group

Robert Krause

Research associate

Robert was awarded his PhD from the University of KwaZulu-Natal. His PhD focused on identifying potential alternative malaria diagnostic target proteins and raising antibodies against these. Of interest were reagents to detect P. knowlesi malaria, for which there is currently no available species-specific antibody-based test. Robert is interested in understanding the role of antibodies and B cells in regulating the immune reaction within TB infected lungs.

Mark Chambers - Leslie Group

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.

Shepherd Nhamoyebonde - Leslie Group

Shepherd Nhamoyebonde

PhD student

Shepherd Nhamoyebonde’s PhD research is to elucidate the role of neutrophils in the immune response and pathogenesis of HIV and M. tuberculosis infections. The project also aims to determine the neutrophil proteomic profile in HIV and TB infected patients in order to identify proteins that will allow prediction of patients with TB.

Magalli Magnoumba - Leslie Group

Magalli Magnoumba

PhD student

Magalli has an MSc in cell biology from the University of Pretoria. She joined the Leslie group in 2018 as a lab technician where she helped in the sorting of tissue resident memory T-cells of tuberculosis infected lung. She is currently pursuing a PhD in immunology, investigating the dynamic perturbation of the T-cell receptor (TCR) repertoire in an HIV longitudinal study.

Mahlatse Maseeme  - Leslie Group

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 - Leslie Group

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.

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.