Competition for polarity influences lymphocyte signaling and function

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/454567

Funding Status
Closed

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Funded Activity Summary

Infectious diseases caused by viruses and bacteria remain a significant health problem. CD46 is a protein on the surface of human cells that is used by a number of viruses and bacteria to enter and infect host cells. Through binding to the CD46 protein, viruses and bacteria can induce changes in immune cells, such as T lymphocytes, that affect the way our immune system responds to infection. For example, immunosuppression induced by infection with measles virus is the primary cause of the mortality and morbidity associated with the disease, and is a phenomenon that is poorly understood. However, there is evidence to suggest that the interaction between measles-infected cells with CD46 on the immune cells is partly responsible for the immunosuppression observed. Our laboratory has recently found that binding of CD46 (by antibody or measles antigen) on immune cells provides a signal to the cell to change its polarisation state (the way proteins are distributed within the cell) and impairs their ability to recognize and kill target cells, and become activated. These observations indicate a new paradigm by which competition of receptor signals for polarization determines signalling outcomes and provides a possible mechanism for how pathogens that bind CD46, such as measles, subvert normal immune cell communication and induce immunosuppression. This proposal aims to investigate the mechanisms behind the effect of polarising signals on immune cells, and will specifically use CD46 and measles virus as a model. The outcomes of this study will define new paradigms in lymphocyte biology and dissect the key pathways that underpin how CD46 influences immune outcome in response to infection.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $500,460.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Immunology

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

T lymphocyte responses | cell polarisation | cell signaling | immune regulation | immunoregulation | lymphocyte | protein localisation | signal transduction | viral immunity | viral infection

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