The Walter and Eliza Hall Institute of Medical Research

Chronic infections

Chronic infections program leader and clinician-scientist: Dr Marc Pellegrini

HIV, hepatitis B virus (HBV) and tuberculosis (TB) are infectious diseases that overwhelm the immune system, leading to chronic infections that are unable to be cleared by the body.

Chronic overwhelming infections, collectively, are the leading cause of years of productive life lost, a measure of premature death due to disease, in the world. Although research has made great inroads into the treatment of these infections, they are still a significant burden of disease: HIV remains incurable; approximately two billion people globally have been infected with HBV; and one third of the world’s population is infected with TB.

The emergence of drug resistance is alarming, particularly following the identification of extensively drug-resistant TB (XDR-TB). These factors underscore an urgent need to find new and more effective therapies that can provide hope for a functional ‘cure’ and prevent the five million deaths that occur globally each year due to these organisms.

Boosting the immune system

Given the ability of these diseases to overwhelm the immune system, Dr Marc Pellegrini and colleagues from the Infection and Immunity division have focused their attention on finding ways of boosting host immunity to help the body clear the infections.

The laboratory's research into the immune signalling hormone (cytokine) IL-7 culminated in the discovery that therapeutic administration of IL-7 was able to cure mice of a chronic overwhelming infection. The company that manufactures this cytokine, Cytheris, is now actively involved in numerous clinical trials examining its efficacy in treating HIV, HBV and hepatitis C virus (HCV) infections.

Searching for new therapeutic targets

The Pellegrini lab is vigorously pursuing translational research aimed at identifying novel therapeutic targets that can boost immune responses to HIV, HBV and TB. To help understand the interactions between the host and these pathogens, the research team has utilised an in vivo model of the human immune system that can be infected with HIV and TB. This powerful system allows the team to determine which human genes help or stunt the immune response to chronic overwhelming infections. The identification of important immune regulatory genes has major implications for the development of therapeutics that can target immune signalling pathways and promote immunity and clearance of infections.

Studying a tuberculosis epidemic

The team is also collaborating with researchers from the Papua New Guinea Institute of Medical Research (PNGIMR) to establish a research site ‘in the field’, in the PNG gulf province of Kikori. This region is the centre of a major outbreak of TB.

The team is conducting clinical epidemiological research to identify the major causes of the epidemic, whilst also performing studies to understand why in some cases the human immune system succumbs to the Mycobacterium tuberculosis bacteria. These studies will provide important information on how the epidemic can be stopped through interventions and also they will provide vital information on which human genes promote clearance of TB.