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Human bodies defend themselves using a diverse population of immune cells that circulate from one organ to another, responding to everything from cuts to colds to cancer. But plants don't have this luxury.

Because plant cells are immobile, each individual cell is forced to manage its own immunity in addition to its many other responsibilities, like turning sunlight into energy or using that energy to grow. How these multitasking cells accomplish it all—detecting threats, communicating those threats, and responding effectively—has remained unclear.

Research from Salk Institute scientists reveals how plant cells switch roles to protect themselves against pathogens. When a threat is encountered, the cells enter a specialized immune state and temporarily become PRimary IMmunE Responder (PRIMER) cells—a new cell population that acts as a hub to initiate the immune response.

The researchers also discovered that PRIMER cells are surrounded by another population of cells they call bystander cells, which seem to be important for transmitting the immune response throughout the plant.

The findings, in Nature on January 8, 2025, bring researchers closer to understanding the plant immune system—an increasingly important task amid the growing threats of antimicrobial resistance and climate change, which both escalate the spread of infectious disease.

"In nature, plants are constantly being attacked and require a well-functioning immune system," says Professor Joseph Ecker, senior author of the study, Salk International Council Chair in Genetics, and Howard Hughes Medical Institute investigator.

"But plants don't have mobile, specialized immune cells like we do—they must come up with an entirely different system where every cell can respond to immune attacks without sacrificing their other duties. Until now, we weren't quite sure how plants were accomplishing this."

Plants encounter a wide range of pathogens, like bacteria that sneak in through leaf surface pores or fungi that directly invade plant "skin" cells. Since plant cells are stationary, when they encounter any of these pathogens, they become singularly responsible for responding and alerting nearby cells.

Another interesting side effect of immobile cells is the fact that different pathogens may enter a plant at different locations and times, leading to varying immune response stages occurring simultaneously across the plant.

With factors like timing, location, response state, and more all at play, an infected plant is a complicated organism to understand. To tackle this, the Salk team turned to two sophisticated cell profiling techniques called time-resolved single-cell multiomics and spatial transcriptomics. By pairing the two, the team was able to capture the plant immune response in each cell with unprecedented spatiotemporal resolution.

"Discovering these rare PRIMER cells and their surrounding bystander cells is a huge insight into how plant cells communicate to survive the many external threats they face day-to-day," says first author Tatsuya Nobori, a former postdoctoral researcher in Ecker's lab and current group leader at The Sainsbury Laboratory in the United Kingdom.

The team introduced bacterial pathogens to the leaves of Arabidopsis thaliana—a flowering weed in the mustard family commonly used as a model in research. They then analyzed the plant's response to comprehensively identify each cell's state upon infection. In doing so, they discovered a novel immune response state, which they called PRIMER, that emerged in cells at specific immune hotspots.

The PRIMER cells expressed a new transcription factor—a type of protein that regulates gene expression—called GT-3a, which is likely an important upstream alarm for alerting other cells to an active plant immune response.

Additionally, the cells surrounding these PRIMER cells proved equally important. Dubbed "bystander cells," the cells immediately neighboring PRIMER cells were expressing genes that enable long-distance cell-to-cell communication.

The researchers plan to elucidate this relationship in future research, but for the time being, they suspect the interactions between PRIMER and bystander cells are key to propagating the immune response across the leaf.

This new spatiotemporal, cell-specific insight into the plant immune response is for researchers worldwide. As pathogens continue to evolve and spread amid climate-related environmental changes and rising antibiotic resistance, the database offers an important springboard for preserving a future filled with healthy plants and crops.

"There is a lot of interest and demand for detailed cell atlases these days, so we're excited to create a new one that is publicly available for other researchers to use," says Ecker.

"Our atlas could lead to many new discoveries about how individual plant cells respond to environmental stressors, which will be crucial for creating more climate-resilient crops."

Other authors include Joseph Nery of Salk; Alexander Monell of Salk and UC San Diego; Travis Lee of Salk and Howard Hughes Medical Institute; Yuka Sakata, Shoma Shirahama, and Akira Mine of the University of Kyoto in Japan.