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PLANT IMMUNITY Mustard Shows Backbone in Its Own Defense Plants, Vertebrates Appear to Share Elements of Innate Immune System In people and other vertebrates, the innate immune system sprints to engage dangerous pathogens for a few days until the more highly evolved adaptive immune response powers up its specialized troops. Fred Ausubel, Jen Sheen, Joulia Plotnikova, Matthew Willmann, Guillaume Tena (left to right, in a rooftop greenhouse), and colleagues detailed the network of signals Arabidopsis plant cells use to detect a pathogen and turn on its defense response. Photo by Steve Gilbert In plants, the innate immune response stands as the full defense between destructive microbes and subsequent disease or death. Over the past few years, accumulated evidence from many labs suggests that plants, animals, and insects share common elements in their innate skirmishes with potential pathogens. In the Feb. 28 Nature, plant scientists at Massachusetts General Hospital and their colleagues have reported another striking similarity. The researchers identified the step-by-step process from the sentry guarding the cell perimeter to the deployment of the defensive immune mechanisms. The details from danger signal to action were worked out in isolated cells of the mustard Arabidopsis thaliana. In the study, leaves infected with bacterial or fungal pathogens stayed green and healthy-looking when the newfound molecular signaling pathway was activated, but the leaves deteriorated with disease and died when the signaling pathway was blocked. The pathway is mediated by a MAP kinase cascade. When it comes to self-defense, plants and animals show similar footwork. First, a receptor on the cell membrane detects the tickle of flagellin on pathogenic bacteria. Inside the cell, protein links and kinase cascades pick up and carry the danger signal to the transcription factor. Then, early immune genes launch a defense response general enough to fight both bacteria and fungi. Step by step, this pathway was detailed for the first time in plants in a Nature paper by Massachusetts General researchers and their colleagues. Apparently conserved from early evolution, the signaling pathway is related to more complex and less well understood innate immune signals in animals. Animals have receptors with similar pathogen-recognition parts, as well as MAP kinase-mediated signaling to transcription factors that kick-start general pathogen-fighting mechanisms. "The exciting part about this work is that it is the first description in plants linking a receptor and MAP kinase signaling cascade to a transcription factor and target genes," said Barbara Baker, a researcher at the University of California, Berkeley, who discovered one of the first plant resistance genes. "The pathway provides further evidence for possible transkingdom connections between plant and animal innate immunity. This study also highlights the importance of MAP kinase cascades as major players in key signaling activity in plants." Immune Targets The innate immune system responds to shared features of different pathogens, such as the tiny flagella that propel bacteria. A couple of years ago, researchers in the Swiss lab of Thomas Boller, a co-author on the paper, discovered the plant cell receptor that recognizes a portion of flagella on pathogenic bacteria. (Since then, other researchers have shown that symbiotic bacteria lack this feature.) Beginning with this receptor, postdoctoral fellows from the neighboring MGH labs of Jen Sheen and Fred Ausubel started probing other aspects of the immune response. When they compared notes, they discovered they were working on different aspects of the same molecular pathway and teamed up. In Ausubel's lab, Tsuneaki Asai, now a scientist at Protein Design Labs in Fremont, Calif., connected the receptor with a downstream transcription factor and early immune response genes. Meanwhile, in Sheen's lab, Guillaume Tena worked out the details of the MAP kinase cascade. "MAP kinase cascades link what happens outside a cell to something inside," Tena said. "Each step in the cascade amplifies the signal from the receptor." Plant Research Reveals Similarities With Animal Kingdom "Up here," says Lance Davidow from a greenhouse atop the Wellman research building at Massachusetts General Hospital, "you never know if a plant on someone's desk is a nice houseplant or a research project." As head of molecular biology bioinformatics at MGH, he is helping Howard Goodman, head of the MGH Department of Molecular Biology, genetically map agronomically important traits in maize, particularly oil yield. Most researchers in the medical community are better acquainted with model systems like yeast, fruit flies, and mice, but three groups in the MGH Molecular Biology Department are using similar molecular and genetic tools to reveal basic biological mechanisms in plants with important potential agricultural applications--and surprising similarities between the plant and animal kingdoms. The rooftop greenhouses are shared by three research groups. Jen Sheen, HMS associate professor of genetics, focuses on how plants respond to different stresses, such as pathogens, salt, cold, and drought. Her group works with the popular model mustard plant, Arabidopsis, and with maize. Fred Ausubel, HMS professor of genetics, studies plant defense responses and how they relate to animal immunity. His group works on Arabidopsis and the worm C. elegans. Finally, Howard Goodman's lab concentrates on genomic technologies and related applications. His group is contributing to the sequencing of the maize genome. The researchers worked with a plant cell system developed by Sheen, HMS associate professor of genetics and senior author of the Nature paper, to study MAP kinase and other signaling pathways. It features plant cells missing their thick protective cell walls, exposing the cell's vulnerable plasma membrane for easy plasmid DNA transformation. The cells are protoplasts (the plant version of stem cells), cued to behave as leaf cells. In one day with this plant system, the researchers can test ideas that might take months or years in classical genetic experiments with whole plants. Growing time and greenhouse space have not been the only hurdles for signal transduction studies in plants. Classic plant genetic studies, such as those with mutants, have failed to reveal such specific immunological pathways in part because of redundant pathways, Sheen said. "Plants are not dummies. If you take out one component, there are others that can respond to the same pathogens." For example, in the Nature paper, the researchers also report finding an alternative non-MAP kinase signaling pathway between the flagellin peptide receptor and the transcription factor, as well as redundant partners through the MAP kinase cascade all the way through to a redundant pair of transcription factors. After the researchers identified the pathway in the protoplast leaf cell system, they verified the pathway in whole leaves using a couple of common pathogens. They used bacteria that can show up as black spots on backyard tomatoes. For the fungal test, plant pathologist Joulia Plotnikova used the most widely spread pathogenic fungus and wandered over to the nearby grocery store for a cabbage. "It looked pristine," she insisted, in defense of the store's reputation. The researchers are following up with studies in whole plants. Sheen predicts the research may eventually lead to ways to engineer plants that are more resistant to diverse pathogens. Early follow-up experiments with mutant plants have resulted in pathogen resistance but also in stunted growth, likely due to the ubiquitous nature of MAP kinase cascades and their role in plant growth and development. "People have assumed plants are completely different from animals, especially at the fundamental level of how they respond to pathogens," said Ausubel, an HMS professor of genetics whose group collaborated on this paper. "The big message is the evolutionary conservation of innate immunity." The Nature paper is the first publication from a $4.5 million, five-year grant to Sheen and Ausubel from the National Science Foundation's plant genome program, a new series of grants designed to promote and fund long-term genomics research projects. Making the final stages of the work a little easier, the 125-million-base sequence of the Arabidopsis genome was completed just over a year ago. It is the first completed higher plant genome and is finished in more detail than that of any other multicellular organism. --Carol Cruzan Morton