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Researchers discover a new immune response mechanism

As part of a Franco-American research effort, teams from the Institut Pasteur, INRA and Inserm have shed light on a cascade of reactions that set off the production of interferon-lambda (IFN-λ). These proteins play an important role in the immune system, especially in intestine, lung and liver cells. Their unexpected production has been linked to cell organelles called peroxisomes, whose main known function is to detoxify cells. This research offers insight into these little-described interferons, which could lead to the development of therapeutic strategies using these proteins.

Human hepatocytes in which a higher number of peroxisomes was induced (detected by the Pex14 marker) through the overexpression of a protein contributing to the development of these organelles (Pex11beta). When these cells are infected by a virus, they overproduce the interferon-lambda.. © INRA, Hélène Bierne
By INRA News Office
Updated on 01/05/2015
Published on 10/24/2014

Interferons (IFNs) are proteins that are synthesised by the body in response to a virus or bacterial infection. They activate the body’s immune system and limit the spread of pathogens, such as by inducing the death of infected cells. IFN-λ is one of three types of known interferons, and the last to have been identified in 2003. It was first studied for its powerful antiviral action. However, in 2012 researchers from the Institut Pasteur, INRA and Inserm showed that it also played a part in the immune response against bacteria(1). IFN-λ, which is still not well understood, primarily acts on epithelial cells that are particularly exposed to bacteria and viruses, such as those in the intestine, liver and lungs.

The tri-institutional team joined forces with researchers from Harvard Medical School to describe the signalling pathway that enables IFN-λ production. They were able to demonstrate the chief role of peroxisomes, a type of cell organelle found in high numbers in epithelial cells. Peroxisomes are well known for their metabolic activities: they are responsible for oxidising various organic molecules and breaking down substances that are harmful to cells, such as free radicals.The Franco-American study identified their important function in the immune system, showing that peroxisomes receive signals from the cell receptors that recognise outside aggressors. The peroxisomes then induce the expression of the IRN-λ protein-coding gene. This cascade of reactions is set off both by viruses such as dengue virus and rotaviruses, which cause gastroenteritis, and bacteria such as Listeria.

The researchers were then able to demonstrate that patients with illnesses related to a lack of or altered peroxisomes showed an impaired immune response set off by the virus.

This research illustrates the double function of peroxisomes and highlights the close link between metabolism and the immune system. It also paves the way to using IFN-λ in therapeutic treatments aimed at strengthening patient immune response.

(1) Bierne et al. Activation of Type III Interferon Genes by Pathogenic Bacteria in Infected Epithelial cells and Mouse Placenta. PLOS ONE, 14 June 2012, DOI:10.1371/journal.pone.0039080

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Charlotte Odendall, Evelyn Dixit, Fabrizia Stavru, Helene Bierne, Kate M. Franz, Ann Fiegen, Steeve Boulant, Lee Gehrke, Pascale Cossart and Jonathan C. Kagan. Diverse intracellular pathogens activate Type III Interferon expression from peroxisomes. Nature Immunology, 22 June 2014. DOI:10.1038/ni.2915.