New pathway in body's immune response uncovered

27 August 2018

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New understanding of one of the body’s immune defence mechanisms could reveal new therapeutic targets for conditions such as cancer and autoimmune diseases, a University of Queensland study has revealed. 

Associate Professor Kate Schroder from UQ’s Institute for Molecular Bioscience and her team uncovered a new line of defence deployed by the immune system against bacteria, in research led by Drs Kaiwen Chen, Mercedes Monteleone and Dave Boucher.

“Bacteria are often quickly killed by a white blood cells called neutrophils, which are the body’s initial line of defence against infection. We discovered an unexpected secondary line of defence, that is deployed against bacteria that have evaded the initial immune response and invaded the neutrophil itself,” Dr Schroder said.

“This new immune defence pathway is mediated by an ‘executioner’ protein called Gasdermin D.”

“This protein drives an unusual form of ‘cellular suicide’, in which the cell extrudes structures called neutrophil extracellular traps, or NETs, that trap the infection and prevent it from spreading.”

NETs are networks of DNA fibres embedded with antimicrobial proteins that immobilise and kill bacteria, providing a secondary line of resistance.

While researchers already knew that neutrophil cell death can be associated with NET expulsion, this discovery revealed an entirely new pathway mediated by Gasdermin D and the inflammasome, a molecular machine that senses and responds to infection.

Dr Schroder said while NETs have a protective role in fighting pathogens, they can also drive pathology in some autoimmune and inflammatory diseases, and cancers. 

“It’s important we understand the basic cellular mechanisms of inflammation before we develop treatments for various immune-related diseases,” Dr Schroder said.

“Understanding how the executioner protein Gasdermin D drives neutrophil death and the explusion of NETs could lead to new therapeutic targets for immune-related diseases, which could in turn lead to more effective treatments and improve quality of life for affected individuals.”

The paper was published in Science Immunology and was supported by the National Health and Medical Research Council of Australia, the Australian Research Council and the Australian Cancer Research Foundation

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