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.
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.
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.
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
THE ROLE OF THE TETRASPANINS CD37 AND CD82 IN LEUKOCYTE MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$370,902.00
Summary
White blood cells must be able to migrate to fight infection. For instance, immune responses are started by the migration of one type of white blood cells to the lymph node. Also, once activated white blood cells migrate out of the circulation to the site of infection where they can kill bacteria and viruses. This grant studies 2 proteins that control white blood cell migration. These proteins may one day be targets for drugs that either promote immunity or reduce inflammation.
Mechanisms Of Alpha-hemolysin Induced Immunoevasion By Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$465,475.00
Summary
S. aureus infections represent a serious global health problem. Currently, no vaccination is available demanding a better understanding of the immune response against this bacterium. We will test the hypothesis that S. aureus alpha-hemolysin represses the migration of innate immune cells to sites of cutaneous infection resulting in diminished immunity. Unraveling the mechanism behind this phenomenon will pave the way to better prophylactic and therapeutic measures against S. aureus infections.
Neutrophil Regulation Of Early Adaptive Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$613,273.00
Summary
The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammator ....The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammatory diseases.Read moreRead less
Inhibition Of Necroptosis As A Novel Strategy For The Prevention Of Bronchiolitis And Subsequent Asthma
Funder
National Health and Medical Research Council
Funding Amount
$658,015.00
Summary
Severe virus associated bronchiolitis is a major cause of infant mortality and a risk factor for asthma. Using a mouse model, we have shown that virus infection causes tissue damage, leading to the release of 'danger' molecules that promote excessive inflammation and tissue remodelling. We have identified an important mechanism by which the danger molecules are released. We will now assess whether blocking this process ameliorates viral bronchiolitis and breaks its nexus with subsequent asthma.
The Identification And Characterisation Of A New DNA Receptor
Funder
National Health and Medical Research Council
Funding Amount
$656,498.00
Summary
The immune system has evolved to fight disease-causing microbes. First, it has to recognize that an infectious agent has invaded. To do this we have developed many probes (receptors) that sense microbial products. Detecting microbial DNA is a critical alarm bell. However, distinguishing pathogen DNA from our own DNA is difficult because both look alike. We have identified a new receptor that helps us identify bacterial DNA and alerts the immune system to the imminent danger.