Human Cytomegalovirus Encoded Control Of The Latent Phase Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$639,871.00
Summary
Human cytomegalovirus has the ability to hide in the body of a person throughout their life time without it making them ill but the virus can awaken (reactivate) from this latent state and produce new virus. In immunosuppressed people such as transplant patients this reactivation causes significant problems, even death, yet this latency remains poorly understood. This project will help us to understand how the virus can hide successfully from the immune system in a latent form in the human host.
Cell Migration And Granuloma Formation In The Expression Of Protective Immunity Against Tuberculosis In The Lung
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
Tuberculosis (TB) remains an enormous problem worldwide and a continuing health problem in Australia. Most TB is not due to disease at the time of infection, but is a reactivation of dormant infection in people who have never eradicated the organisms. This study will investigate, in mice, how TB is initially contained within the lungs and how reactivation occurs. All mice infected with TB control the infection initially. T lymphocytes are activated and T cells and macrophages are recruited to th ....Tuberculosis (TB) remains an enormous problem worldwide and a continuing health problem in Australia. Most TB is not due to disease at the time of infection, but is a reactivation of dormant infection in people who have never eradicated the organisms. This study will investigate, in mice, how TB is initially contained within the lungs and how reactivation occurs. All mice infected with TB control the infection initially. T lymphocytes are activated and T cells and macrophages are recruited to the lung, migrate into lung tissue and surround infected lung macrophages forming granulomas. We have identified mice that progress to TB disease early after infection (early progressor strains) and another strain that progresses later (late progressors). In the early progressors, lymphocytes are not as efficiently recruited to the lung and do not form the tight granulomas seen in late progressor strains. We plan to make a detailed comparison of these two strains looking at differences in cell-membrane molecules and the soluble messenger molecules (cytokines and chemokines) that provide the signals that attract cells to the lung and direct them to surround infected lung macrophages. By comparing events in early and late progressor strains we will find which molecules are required for initial and long-term containment, and which events lead to breakdown of granulomas and reactivation of disease. In addition, we recently showed that one cytokine, tumour necrosis factor (TNF), is essential for cell migration through the lung. By comparing normal mice with mice deficient in TNF we will study the downstream effects regulated by TNF, particularly the chemokine messengers that direct cell movement into granulomas. By identifying the molecules and cells required to control TB we plan to design improved vaccines to prevent TB infection and improved treatments to prevent disease reactivation.Read moreRead less
Cytokine And Macrophage Determinants Of Pulmonary Inflammation During Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$455,899.00
Summary
Tuberculosis (TB) infects 33% of the world, causing over 2 million deaths per year. TB disease causes damaging lung pathology and new therapies to treat the infection and moderate inflammation are urgently required. TNF is essential for immunity to TB, acting to modulate inflammation. This grant will determine how soluble and membrane- bound TNF regulate the cellular and cytokine control of TB pathology and may lead to new therapies to limit inflammation in TB and other inflammatory diseases.