Recruitment and activation of alternatively activated macrophages by thioredoxin peroxidases in helminth infections

Funded Activity Summary

This research will unlock the immunological steps that lead to the development of pathological consequences associated with infectious pathogens and human diseases. The investigation proposed is very timely, as there is a rapid growth in people acquiring infectious diseases in the developing world and inflammatory pathologies in the developed world such as artherosclerosis, asthma, and tumour progression. There is a common denominator between all of these diseases. The body loses its ability to regulate a particular type of immune response, termed Th2. This results in the production of a chronic inflammation, which causes lasting damage. We have previously pinpointed the activity of a particular type of white blood cell, the macrophage, as pivotal to the induction of the Th2 immune response. We have also identified a molecule, thioredoxin peroxidase (TPx) that triggers the macrophage to switch on Th2 responses. Once the TPx comes into contact with the surface of the macrophage cell, a series of proteins, called transcription factors become activated in a controlled cascade. This leads to the secretion of substances from the macrophage, which signal the development of Th2. We will identify the mechanism that TPx uses to initiate the process. We propose to investigate this sequence of events by using an in-vitro cell based model to study the enzymatic steps as the macrophage responds to TPx. This goal represents much more than scientific curiosity. A better understanding of the process may reveal how TPx switches on the macrophage. If the trigger for this could be found, it would present a new way to manipulate the macrophage. This will possibly unearth new drug targets and lead to more effective therapeutics against infectious diseases, asthma, artherosclerosis and cancer.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $243,000.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Immunology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Th1/Th2 cells | cell-cell communication | disease models, animal | immune regulation | immunomodulation | innate immunity | macrophage activation | parasite infection | parasitology | therapeutic targets

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