Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers ar ....Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers are infected throughout an infected person's life and that they remain infected despite years of treatment with potent combination drug therapies which reduce the amount of virus in the blood to undetectable levels. We have evidence that suggests that a certain subset of monocytes may be preferentially infected with HIV and may contribute significantly to its persistence in the body. This subset is known to be expanded in response to certain infections, probably including HIV, and during inflammation. We have shown that these cells accumulate in the brains of HIV-infected people especially those with AIDS related dementia. In this project we will characterise these cells in the blood and test our hypothesis that ongoing infection in this subset of monocytes plays an important role in the course of HIV disease and contributes to the persistence of HIV infection and the failure of currently available therapies to eradicate it.Read moreRead less
I am a physician-scientist whose research involves the role of monocyte-macrophages in HIV pathogenesis and low cost methods for monitoring HIV infection in resource-constrained countries
This project will determine how viruses prevent transmission of messages within cells which orchestrate responses of our immune system to infection and whether our current therapies improve this defect. This knowledge will help us to better understand why our immune system is not able to control chronic virus infection and improve therapies for these diseases.
Translating Research Into HIV-related Health Outcomes In The Developing World
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
Professor Crowe's research addresses important health issues for HIV infected people living in resource limited countries. Her team validates low cost point of care tests to monitor HIV infection, including a test she co-developed to determine when to start anti-HIV treatment, and investigates how these low cost tests can improve clinical care of people with HIV and TB. In addition she will determine how changes in the immune system increase the risk of heart attacks in young HIV patients.
Genetic Modulation Of The Host Response To Pulmonary TB
Funder
National Health and Medical Research Council
Funding Amount
$540,273.00
Summary
Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host respo ....Tuberculosis (TB) is an enormous global health problem. The World Health Organisation estimates that TB, which is caused by infection with the bacteria Mycobacterium tuberculosis, infects 2 billion individuals, leading to 2 million deaths and 8 million new cases of disease per year. Most TB disease is not manifest at the time of infection, but is a reactivation of latent disease in people who do not completely eradicate the primary infection. In a latent infection an effective chronic host response contains dormant TB organisms inside activated macrophages. Cells are recruited to wall off infected macrophages and specific T cells continually induce the activate state with minimal tissue damage (immunopathology). Although currently available antibiotics can kill TB organisms, the treatment is prolonged, expensive, difficult to administer in poorly resourced regions and not effective against multi-drug resistant organisms. New therapies to treat both active disease and prevent reactivation in individuals who are latently infected are urgently required. This proposal will address this problem using a novel approach, namely gene manipulation to augment host immunity to TB and limit concurrent immunopathology. We will construct vectors to increase expression of the key immune molecules, the T lymphocyte activating cytokines IL-12 and IL-23, and the macrophage effector molecules LRG-47 and Indoleamine 2,3-Dioxygenase (IDO). These molecules are known to be involved in TB killing. We will determine if increasing their expression increases the killing capacity of TB-infected macrophages and we will examine how these molecules interact to aid clearance of the TB bacilli. This internationally competitive grant will further our detailed understanding of the complex immune response to TB organisms and lead to the development of novel therapies to treat TB infection and prevent reactivation of latent disease.Read moreRead less