The Role Of Perivascular Macrophages In The Regulation Of Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Neutrophils are key defenders against bacterial infections. In this application we will test the hypothesis that perivascular macrophages play a critical role in the recruitment of neutrophils to site of cutaneous infection, and that these cells are targeted and destroyed by bacterial virulence factors. Our studies will gain novel insight into the leukocyte homing paradigm and shed new light on the mechanisms of microbial immuno-evasion.
To Describe The Regional Differences In The Innate Immune System Of The Skin Using Intra-vital Multiphoton Microscopy And Understand Its Functional Consequences In A Cutaneous Parasite Infection Model.
Funder
National Health and Medical Research Council
Funding Amount
$97,182.00
Summary
This study is the first of its kind to map the innate immune system, the body's first line of defence, in the skin - coined the "immune atlas". Researchers have shown regional differences in innate immune cells which could explain how infections develop at different sites of the body. Although they have shown this in a cutaneous leishmaniasis model, a parasite endemic in most parts of the world, it may have implications also for inflammatory skin conditions such as eczema or psoriasis.
Dynamics And Mechanisms Of Neutrophil Migration During Tissue Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
Neutrophil granulocytes are central mediators of inflammatory conditions and infections. It is currently unclear how neutrophils navigate through inflamed tissues and how they detect damaged cells and/or pathogens. This proposal will use cutting-edge multi-photon microscopy to dissect the dynamics and mechanisms of neutrophil behaviour in real time in living animals. These experiments will provide a new understanding of the development of inflammatory diseases.
Age-dependent Regulation Of Type 2 Immunity By Dermal Innate Lymphoid Cells
Funder
National Health and Medical Research Council
Funding Amount
$609,281.00
Summary
Type 2 immune responses are critical for the defense against worm infections, but can also cause allergic reactions. How type 2 immunity is regulated is poorly understood. The aim of this application is to define the function of a newly discovered skin immune cell population, dermal type 2 innate lymphoid cell, in cutaneous worm infections and allergies. We anticipate that our studies will aid in the development of strategies to prevent or treat skin allergies and parasitic infections.
Mammals have evolved an array of mechanisms to sense microbes. These immune sentinels must distinguish self from non-self to activate an immune response. The initiation, amplification and quenching of an immune response is carefully orchestrated to eliminate invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that prevent inflammatory diseases such as cardiovascular disease, hepatitis, inflammatory bowel disease and skin diseases.
Many white blood cells have an innate ability to sense infection, and trigger inflammation to fight invading microbes. These innate immune cells use particular receptors to sense pathogens and we have now identified a new pathway that leads to the activation of one of these, known as Pyrin. Genetic mutations can activate this pathway, and our project will determine the molecular basis for this, and how it can be targeted to treat inflammatory disease.
Initial Interactions Of Herpes Simplex Virus With Innate Immune Cells In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$522,589.00
Summary
Herpes simplex viruses 1 and 2 cause widespread and occasionally serious diseases including genital herpes, neonatal death and encephalitis. Current vaccine candidates are at best partially effective. This grant will examine the way that the virus enters, initially spreads within the skin and interacts with immune cells to help determine which cells should be stimulated by vaccines.