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.
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.
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.
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.
Understanding The Host Pathogen Relationships Of Hendra Virus In Bats, Horses And Humans
Funder
National Health and Medical Research Council
Funding Amount
$648,339.00
Summary
We will examine why bats can be infected with Hendra Virus with no apparent symptoms, yet the virus causes severe disease in other mammals including humans. We will examine the innate immune response towards the virus in the natural host (fruit bats), horses and humans. In addition to the innate immune response we will also examine the adaptive immune response in bats and humans. We hope this information can be used to design new drugs or vaccines to Hendra Virus.
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.
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.
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
Argonaute Proteins In The Mammalian Antiviral Response
Funder
National Health and Medical Research Council
Summary
Viruses are the most abundant infectious agents on earth, and the diseases caused by them are a constant threat and cause of mortality worldwide. Awarded the Nobel Prize for Medicine in 2006, RNA interference (RNAi) is a natural process that plants use to attack viruses. Humans possess all of the tools for RNAi, but whether it is used for antiviral defense is unknown. This study aims to uncover this immune process which will open new avenues to treat virus infections, such as influenza and HIV.
Understanding The Role Of MAIT Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,593.00
Summary
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells protect us from bacteria and yeast at mucosal sites where the body's immune defences are most easily breached, e.g. gut, oral cavity, airways & reproductive tract. This study investigates the role of MAIT cells in health and in diseases like inflammatory bowel disease, peptic ulceration, periodontitis and tuberculosis. Controlling MAIT cells could help in treating these conditions.