Combating Infectious Diseases By Harnessing Macrophage Functions
Funder
National Health and Medical Research Council
Funding Amount
$688,152.00
Summary
Infectious diseases present a persistent global health threat. For patients with life-threatening diseases caused by bacterial pathogens, antibiotics provide the last resort. Antibiotic resistance, even for newly developed antibiotics, is widespread within the bacterial community. New strategies are urgently needed to combat most bacterial infections. This proposal will investigate a new strategy to train and boost our immune systems to combat infectious diseases.
The Role Of IL-17 In Regulating Liver Macrophage Permissiveness For Leishmania Infection
Funder
National Health and Medical Research Council
Funding Amount
$655,082.00
Summary
Visceral Leishmaniasis is a disease of poverty in the developing world caused by Leishmania parasites, which live and replicate within host tissue macrophages. A cytokine produced by host cells, IL-17A impairs the ability of liver macrophages to control this infection, as mice that lack IL-17A have lower parasite burdens in the liver after experimental infection. We propose to investigate if IL-17A mediates this impaired control by tuning the permissiveness of host macrophages to infection.
Elucidating The Critical Roles Of ILC1, NK Cell And Innate Memory In Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$657,024.00
Summary
Natural killer cells are innate cells that provide first line defense against infection and cancer. The recent discovery of a novel innate cell population has modified our vision of the early events necessary for immune protection. Understanding the role of these cells is critical as they could represent viable therapeutic targets. We have developed unique mouse models to experimentally target this population to determine how they are generated and their role in combating infection and cancer.
As the first recruited cells, neutrophils direct protective responses against infection, but can also mediate destructive responses in inflammatory disease. This project will determine mechanisms driving neutrophil-dependent inflammation in both settings, by examining a specific inflammation-promoting molecular pathway (the ïinflammasomeÍ) in neutrophils. This research will lead to a better understanding of inflammation, and may suggest therapeutics for treating inflammatory disease.
Recognition And Interaction Of Virus By The Innate Immune System
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
The innate immune system acts rapidly to limit infection of invading pathogens. The interaction and recognition of pathogens such as viruses by the innate immune system, is of importance to understand why particular pathogens induce disease.
Characterization Of Human-specific Anti-microbial Pathways
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The immune system protects us against infectious disease by killing invading microbes or pathogens. Macrophages are white blood cells that are important for the recognition and destruction of pathogens. This project aims to investigate the role of certain genes, which are turned on in macrophages when they sense invading pathogens, in protecting us against infectious diseases such as tuberculosis and gastroenteritis.
Cytoplasmic DNA As A Danger Signal For Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
DNA in mammalian cells is contained within a structure known as the nucleus. The presence of DNA outside the nucleus in the cytoplasm of the cell is a sure sign that something is wrong, and may indicate the presence of a viral invader. In this case, the cell initiates anti-viral responses, including production of anti-viral proteins and death of the infected cell to stop replication of the virus. Lack of proper control of these responses may contibute to the autoimmune disease lupus.
Pattern Recognition Receptors In Inflammation And Infection
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Innate immunity provides our first line of defence against infections, but pathogens can overcome this system. Understanding how microbes disable innate immunity can teach us how to prevent and/or treat infectious diseases. Innate immunity acts by initiating inflammation. Many important acute and chronic diseases develop when this process is dysregulated. Blocking innate immunity thus has potential to treat many diseases. This project aims to understand innate immunity in these contexts.
Defining The Role Of Zinc In Human Macrophage Responses To Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$592,049.00
Summary
It is estimated that one third of the worlds population is affected by mild to moderate zinc deficiency, and that this predisposes to a range of infectious diseases. The immunomodulatory effects of zinc have been appreciated for many years, and indeed zinc supplementation is used to treat severe diarrhoeal diseases. This project aims to understand the anti-infective mechanisms of zinc by focusing on macrophages, a key cell type involved in killing invading microorganisms.
The Host Response To Highly Pathogenic Influenza Virus
Funder
National Health and Medical Research Council
Funding Amount
$237,981.00
Summary
Highly pathogenic influenza infections are a global health concern and cause global panic. There is no effective therapy available; for example and the death rate for H5N1 infection is ~60%. Here we propose to further understand host lung response to highly pathogenic influenza with a view to develop new therapies for this urgent issue.