Press releases
Please quote Nature Immunology as the source of these items.
The August 2008 issue of Nature Immunology is available online.
August 2008
New anti-parasite protective mechanism
Scientists have discovered how the immune system fights Toxoplasma gondii, a parasite that causes the disease toxoplasmosis in humans, according to a paper online this week in Nature Immunology.
Immune cells called CD8+ T lymphocytes are required to fight T. gondii, which can cause severe disease in humans with weak immune systems. These cells recognize parasite-derived protein fragments displayed on the surface of infected cells. Nilabh Shastri and colleagues show that a fragment of the T. gondii protein called GRA6 is a target of CD8+ T lymphocytes and induces a protective immune response in mice.
They also showed that the host cell protein ERAAP, which acts as a scissor to 'clip' proteins into fragments, is required for the production of this protective GRA6 fragment. This is the first time ERAAP has been shown to have a specific and protective role in the immune response to pathogens.
Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum
Nicolas Blanchard, Federico Gonzalez, Marie Schaeffer, Nathalie T Joncker, Tiffany Cheng, Anjali J Shastri, Ellen A Robey & Nilabh Shastri
Published online: 29 June 2008 | doi 10.1038/ni.1629
Constraining neutrophil damage
The way in which neutrophils – the immune system's 'first responders' – migrate into target tissues is reported online this week in Nature Immunology.
Neutrophils are the 'look-out' white blood cells that can exit the bloodstream at the first sign of infection and travel to its source. Here they can release their payload of noxious chemicals in an attempt to stave off the invaders.
Jingsong Xu and colleagues identify an intracellular signaling molecule, called MYLK, that is required for neutrophil movement. MYLK links the 'danger' signals sensed outside cells to their intracellular structure, allowing them to change shape and direction, as well as increasing their 'adhesive' properties needed to crawl through blood vessels.
Xu's group shows MYLK-deficient neutrophils are less able to enter lung tissues in response to septic infections. However, this defect is not a bad thing as neutrophil-mediated collateral damage is the leading cause of acute respiratory distress syndrome (ARDS), a potential lethal complication of sepsis-induced lung injury. By identifying the signaling pathway between MYLK and the cell structure, scientists can start to develop potential new targets for treating ARDS.
Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating β2 integrins
Jingsong Xu, Xiao-Pei Gao, Ramaswamy Ramchandran, You-Yang Zhao, Stephen M Vogel & Asrar B Malik
Published online: 29 June 2008 | doi 10.1038/ni.1628
Ingesting and digesting intracellular bacteria
Scientists have revealed the importance of autophagy – a process in which cells 'eat' and degrade their own internal contents – in defence against harmful intracellular bacteria.
Previous work linking autophagy with resistance to dangerous bacteria was performed in cells in culture dishes, but experiments failed to identify germ sensors capable of triggering the process.
Online this week in Nature Immunology, Shoichiro Kurata and colleagues show that in fruit flies, PGRP-LE – a protein capable of recognizing specific bacterial components – is required for the induction of autophagy after infection with an intracellular bacterium. This induction of autophagy is also necessary for survival of infected flies.
Whether similar sensors exist and link bacterial infection with autophagy in mammalian cells remains to be determined.
Autophagic control of listeria through intracellular innate immune recognition in drosophila
Tamaki Yano, Shizuka Mita, Hiroko Ohmori, Yoshiteru Oshima, Yukari Fujimoto, Ryu Ueda, Haruhiko Takada, William E Goldman, Koichi Fukase, Neal Silverman, Tamotsu Yoshimori & Shoichiro Kurata
Published online: 06 July 2008 | doi 10.1038/ni.1634
A common inflammatory pathway in silicosis and Alzheimer's
Two different chemical agents, one associated with Alzheimer's, the other with a severe lung disease, cause inflammation in the same way, report two studies published online this week in Nature Immunology. This finding could provide a therapeutic target for the treatment of these diseases.
Many structurally diverse molecules, including bacterial toxins and various crystals such as silicon dioxide that cause silicosis in the lungs, induce inflammation by activating a protein complex inside cells called the inflammasome. Groups led by Eicke Latz and Douglas Golenbock show that silicon dioxide crystals and the form of beta-amyloid protein linked to Alzheimer's disease are taken up by cells in a way that produces inflammation. This process involves seepage of the cathepsin B protein from compartments called lysosomes, which destroy cellular debris. The release of cathepsin B triggers the uncontrolled immune responses associated with silicosis and Alzheimer's disease.
Characterizing this signalling cascade, which is very likely to be associated with other inflammatory diseases such as gout, may thus provide a common target for treatment of a myriad of conditions.
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung, Franz Bauernfeind, Annett Halle, Eivind O Samstad, Hajime Kono, Kenneth L Rock, Katherine A Fitzgerald & Eicke Latz
Published online:11 July 2008 | doi 10.1038/ni.1631
The NALP3 inflammasome is involved in the innate immune response to amyloid-β
Annett Halle, Veit Hornung, Gabor C Petzold, Cameron R Stewart, Brian G Monks, Thomas Reinhecke, Katherine A Fitzgerald, Eicke Latz, Kathryn J Moore & Douglas T Golenbock
Published online:11 July 2008 | doi 10.1038/ni.1636
