Dr Anna Coussens, Lab Head | WEHI Researcher Profile

Q: Cell death in TB, HIV and COVID-19

Our analysis of whole blood transcriptional and epigenetic signatures from TB, HIV and COVID-19 patients has identified the role of multiple cell death pathways in disease risk. We use in vitro infection models of primary human monocyte-derived macrophages and neutrophils to investigate the regulation of pyroptosis, apoptosis and extracellular trap formation during TB, HIV and SARS-CoV-2 infection. We use a variety of molecular techniques, coupled with single-cell analysis by confocal microscopy, super-resolution microscopy, Totalseq, and spectral cytometry to identify the regulators of these pathways and their impact on inflammatory programmed cell death. We are also testing numerous small molecule inhibitors to prevent death via these different pathways.

Q: M. tuberculosis strain variation in TB pathogenesis

Humans have co-evolved with Mycobacterium tuberculosis (Mtb), such that different strains can be found in different regions of the world, and these have been classified into ancient and modern lineages. Some ‘modern’ strains have been shown to be more inflammatory than others. We are testing whether genetic variations in lipid metabolizing genes which would affect the bacterial cell wall, as well as secreted virulence factors under the control of various ESX systems, cause some strains to be hyper-inflammatory. We are investigating the effect of strains with interesting genetic and inflammatory phenotypes on their ability to modulate the composition of phagocyte cell membranes as well as impact the replication co-infecting viruses (HIV-1 and SARS-CoV2). We also study whether the ability of different Mtb strains to cause greater tissue-destructive cell death associates with differences in pulmonary and extra pulmonary TB presentation.

Q: Identifying biomarkers of subclinical TB

Working in South Africa, we are currently conducting a household contact study of individuals who live with people with drug-resistant TB. Using a highly sensitive screening technology called 18Fluorodeoxyglucose positron emission and computerised axial tomographic scanning (PET/CT), we are identifying household members with subclinical stages of infection. This is imaging on their lungs or lymph nodes which may indicate they have a current infection, whilst they have not yet developed symptoms of disease. We are using whole genome RNAseq and DNA methylation analysis to develop and validate a biosignature for recent infection or re-infection that may be of great utility for clinical studies designed to test preventative therapies.

Q: Vitamin D host-directed therapy for TB-HIV

We have shown that deficiency in serum vitamin D impairs the innate and adaptive immune responses to M. tuberculosis and HIV infection, increasing pathogen replication in infected cells and increasing a broad inflammatory response. In order to understand the mechanism of vitamin D regulation we are studying the seasonal changes in DNA methylation in blood cells and how vitamin D supplementation modifies these epigenetic changes. With the idea that vitamin D can enhance innate immunity to prevent M.tb infection, we are collaborating on a Phase III Trial randomizing 5400 children to receive either weekly vitamin D or placebo, for three years. We are investigating whether and how vitamin D modifies the ability of innate and adaptive immune cells from these children to control bacterial replication.

About

Hon A/Prof Coussens, BSc (Hons) PhD, is an infectious disease immunologist whose research focuses on identifying mechanisms and mediators of immune dysregulation that increases risk of developing tuberculosis (TB), leveraging these to develop improved diagnostic and treatment approaches. Over the last 15 years she has characterized the in vivo, ex vivo and in vitro mediators of human TB immunopathogenesis, detrimental co-infection interactions with HIV-1 & SARS-CoV-2, identified and evaluated novel blood biomarkers of subclinical TB, developed bioinformatic tools to improve drug resistant TB detection, and evaluated host-directed therapies to prevent and resolve TB in Phase 2 and 3 clinical trials and experimental medicine studies.

Laboratory Head in the Infectious Diseases and Immune Defence division at the WEHI, since 2018, she previously worked in the UK (2008-2012) and South Africa (2012-2018) and maintains an Honorary Associate Professor position at the University of Cape Town, South Africa. Completing a PhD in Molecular Cell Biology at the Queensland University of Technology (2007) she completed postdoctoral training at the National Institute of Medical Research, UK, working on a Phase 2 TB treatment trial of adjunct vitamin D. In 2012, she moved to University of Cape Town to gain clinical TB-HIV research experience in a high endemic setting, where her innovative work was recognised by the Academy of Science of South Africa in 2014, when she received the Sydney Brenner Postdoctoral Award, an endowment of the late Nobel Laurette.

In 2023, together with colleagues from the UK she initiated and co-chaired the International Consensus for Early TB group, developing a new disease framework for TB. In 2024 she worked with the WHO to progress this into policy change, with asymptomatic TB now defined as a distinct diagnosable state. She has contributed to NIH high level meetings framing the direction of the TB-HIV-Diabetes research agenda, spoken at the Global Research Council on gender equality, World Economic Forum Africa and Wellcome Research Institute on ECR challenges and is an elected member and now alumnus of the Global Young Academy (tenure 2014-2019).

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Selected publications from Dr Anna Coussens

Macpherson L, Kik SV, Quartagno M, Lakay F, Jaftha M, Yende N, Galant S, Aziz S, Daroowala R, Court R, Taliep A, Serole K, Goliath RT, Davies NO, Jackson A, Douglass E, Sossen B, Mukasa S, Thienemann F, Song T, Ruhwald M, Wilkinson RJ, Coussens AK, Esmail H, Barry CE, Ellner JJ, Flynn JL, Heinsohn T, Horsburgh CR, Jacobson KR, Malherbe ST, Salgame P, Sheerin D, Streicher E, Tlala M, Via LE, Walzl G, Warren R, Warwick J. Diagnostic Accuracy of Chest X-ray Computer-Aided Detection Software for Detection of Prevalent and Incident Tuberculosis in Household Contacts. Clinical Infectious Diseases. 2025;80(3):10.1093/cid/ciae528

Munro JE, Coussens AK, Bahlo M. TBtypeR: Sensitive detection and sublineage classification of Mycobacterium tuberculosis complex mixed-strain infections. Communications Biology. 2025;8(1):10.1038/s42003-025-07705-9

Auld SC, Barczak AK, Bishai W, Coussens AK, Dewi IMW, Mitini-Nkhoma SC, Muefong C, Naidoo T, Pooran A, Stek C, Steyn AJC, Tezera L, Walker NF. Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium.American Journal of Respiratory and Critical Care Medicine. 2024;210(8):10.1164/rccm.202402-0374so

Coussens AK, Zaidi SMA, Allwood BW, Dewan PK, Gray G, Kohli M, Kredo T, Marais BJ, Marks GB, Martinez L, Ruhwald M, Scriba TJ, Seddon JA, Tisile P, Warner DF, Wilkinson RJ, Esmail H, Houben RMGJ, group ICFET, Alland D, Behr MA, Beko BB, Burhan E, Churchyard G, Cobelens F, Denholm JT, Dinkele R, Ellner JJ, Fatima R, Haigh KA, Hatherill M, Horton KC, Kendall EA, Khan PY, MacPherson P, Malherbe ST, Mave V, Mendelsohn SC, Musvosvi M, Nemes E, Penn-Nicholson A, Ramamurthy D, Rangaka MX, Sahu S, Schwalb A, Shah DK, Sheerin D, Simon D, Steyn AJC, Anh NT, Walzl G, Weller CL, Williams CM, Wong EB, Wood R, Xie YL, Yi S. Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise. The Lancet Respiratory Medicine. 2024;12(6):10.1016/s2213-2600(24)00028-6

Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR. Influence of individuals’ determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination. npj Vaccines. 2024;9(1):10.1038/s41541-024-00878-0

Savulescu AF, Peton N, Oosthuizen D, Hazra R, Rousseau RP, Mhlanga MM, Coussens AK. Quantifying spatial dynamics of Mycobacterium tuberculosis infection of human macrophages using microfabricated patterns. Cell Reports Methods. 2023;3(11):10.1016/j.crmeth.2023.100640

Sheerin D, Abhimanyu, Peton N, Vo W, Allison CC, Wang X, Johnson WE, Coussens AK. Immunopathogenic overlap between COVID-19 and tuberculosis identified from transcriptomic meta-analysis and human macrophage infection. iScience. 2022;25(6):10.1016/j.isci.2022.104464

Houben RMGJ, Esmail H, Cobelens F, Williams CML, Coussens AK. Tuberculosis prevalence: beyond the tip of the iceberg. The Lancet Respiratory Medicine. 2022;10(6):10.1016/s2213-2600(22)00184-9

Waters R, Ndengane M, Abrahams M-R, Diedrich CR, Wilkinson RJ, Coussens AK. The Mtb-HIV syndemic interaction: why treating M. tuberculosis infection may be crucial for HIV-1 eradication. Future Virology. 2020;15(02):10.2217/fvl-2019-0069

Seddon JA, Chiang SS, Esmail H, Coussens AK. The Wonder Years: What Can Primary School Children Teach Us About Immunity to Mycobacterium tuberculosis?. Frontiers in Immunology. 2018;9:10.3389/fimmu.2018.02946

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Lab research projects

Cell death in TB, HIV and COVID-19

M. tuberculosis strain variation in TB pathogenesis

Identifying biomarkers of subclinical TB

Vitamin D host-directed therapy for TB-HIV

Dr Anna Coussens

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