Dr Al Leslie’s work is devoted to understanding the relationship between HIV and its host, focussing on immune cells’ earliest response to the pathogen. Recently, he’s expanded those studies to include the tuberculosis-causing bacteria Mycobacterium tuberculosis. Al initially trained in agricultural science. He went on to do a PhD in HIV Immunology at Oxford University after witnessing first-hand the devastation wrought by HIV in the late 1990s while he was working in Malawi. Al took up a position as an Investigator at the KwaZulu-Natal Research Institute for TB-HIV in 2012. He is a member of AHRI Faculty, where his lab works to understand how human cells respond to infection with HIV and tuberculosis.
Click here for a full list of publications.
Dr 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
Research Collaborator - Oxford University
Julia Roider is a medical doctor from Germany who is specialising in internal medicine and infectious diseases. Julia is also a member of Professor Philip Goulder’s HIV Research Group at Oxford University. Her work at AHRI seeks to characterise the UKZN HIV Pathogenesis Programme’s Paediatric Slow Progressor cohort further to gain a deeper understanding of the role of T-cell immunity in successful long-term immune control of HIV infection.
Postdoctoral Research Fellow
Ilke completed her PhD (Biochemistry and Biotechnology) with the University of Pretoria and Ghent University, where she conducted research in the Laboratory of Molecular Immunology. Her PhD work investigated how Mycobacterium tuberculosis-associated synthetic mycolic acids affect lipid homeostasis in murine host macrophages. Before joining AHRI, Ilke exploited gene therapy to study epigenetic modifications related to chronic HBV infection at Wits University. She currently investigates adaptive immunity in a 3D model of human granuloma formation.
Amanda Wellmann holds an honours degree from UKZN. For her PhD project, Amanda is working under the mentorship of Dr Henrik Kløverpris, studying possible roles of Innate Lymphoid Cells in tuberculosis pathology.
Paul Ogongo holds a Master of Science (Molecular Medicine) degree from Jomo Kenyatta University of Agriculture and Technology. Paul’s PhD research is the study of T cell immune responses to M. tuberculosis in human lung tissue. The project aims to determine the differences in T cell responses at the infection site and in circulation in order to better inform TB vaccine design.
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.
Mohamed completed his MSc in Medical Biology at the VU University of Amsterdam and joined the Leslie lab in late 2016. His PhD project examines the human innate immune response to M. tuberculosis. In order to mimic granuloma development in the lung, Mohamed will make use of a novel 3D culture model. The model provides a platform on which to study host-pathogen interactions in a more complex tissue-like context.
Lerato Ndlovu did her masters in Plant Breeding and Biochemistry before moving to Dr Al Leslie’s immunology lab at AHRI. The change was inspired by wanting to be part of the solution when it comes to TB and HIV. Her project looks at a set of innate immune cells called neutrophils, which are activated during bacterial infections. She’s interested in investigating their unique phenotypic and genetic signature as a potential biomarker for TB disease status.
Research Lab Technician
Abigail Ngoepe was awarded a Master’s degree from the University of Pretoria. Her work at AHRI aims to determine if there is any relationship between antigen diversity in lymph node germinal centers and the generation of broadly neutralising antibodies in HIV infected infants.
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.