Researchers discover a mechanism that helps immune cells invade tissues

While in the image above the immune cells (bright green) are able to invade the tissues of the Drosophila embryo in the upper central side, they are less successful when their protective envelope is weakened (photo below). Credit: © Stephanie Wachner / IST Austria

To fight infections and heal injuries, immune cells need to enter tissues. They also need to invade tumors to fight them from within. Scientists from the Siekhaus group at the Institute of Science and Technology (IST) in Austria have now discovered how immune cells protect their sensitive guts while compressing them between tissue cells. With their study published in the journal Biology Plus The team lays the groundwork for identifying new targets in cancer treatment.

It is difficult to know exactly when the immune cells will attempt to invade the tumor. In order to study the cell invasion process in detail, scientists like Professor Daria Seckhaus and her team need something more reliable. That’s why they turn to fruit fly embryos. As these embryos develop, macrophages, the dominant form of immune cells in Drosophila, move from where they are born to where the invading tissues are needed. They do so at a certain time, enabling scientists to study the process inside these tiny, transparent animals. With the help of IST Austria’s state-of-the-art bio-imaging facility, they watch macrophages — marked with green fluorescent protein — make their way into tissues.

making armor

The cellular changes needed for this purpose and which genes lead to such changes are still largely unknown. With their new study by first authors Vera Belyaeva, Stephanie Wachner and Attila Giwerje, Siekhaus’ group sheds light on this essential process in health and disease. “Previously, we found that a specific gene, called Dfos, is enriched in immune cells and we wondered what it did,” Seckhaus says.

“Now we can demonstrate that it leads to actin filament aggregation.” These protein strands are concentrated within the cell membrane, also known as the cell cortex, giving the cell surface stability. Scientists have shown that through a complex cascade involving different proteins, actin filaments become denser and more closely connected to each other, forming a stable envelope. “We hypothesize that this acts like a reservoir, distorting surrounding cells while protecting the immune cell’s nucleus from mechanical stress as it invades tissues,” explains Seckhaus. Furthermore, the team was able to demonstrate that the loss of this actin envelope makes it more difficult for immune cells to infiltrate unless the surrounding tissues become softer.

Using the latest technology, scientists at IST Austria can study the process of cell invasion in live Drosophila embryos. (Macrophages in green, surrounding tissue cells in purple). Credit: © Vera Belyaeva / IST Austria

Strengthening immune cells to fight cancer

Although Drosophila and vertebrates like mice and humans do not have much in common at first glance, there are many similarities in the way their genes work. Working with Professor Maria Sibelia of the Medical University of Vienna, researchers at IST Austria found evidence that the vertebrate Fos gene, the equivalent of the Drosophila gene Dfos, activates the same genetic pathways. “We think the same mechanism we found in Drosophila also plays a role in vertebrates,” says biologist Daria Seckhaus.

This raises hope that the group’s findings can help identify new targets for cancer treatment. In the field of immuno-oncology, researchers are looking for ways to activate the body’s immune system to attack the tumor. One of the challenges they face, however, is enabling immune cells to infiltrate the tumor. Siekhaus concludes, “If one can strengthen its protective sheath, it may be easier for it to invade the tumor tissue.”

Cells alter tension to facilitate penetration of tissue barriers

more information:
Belyaeva V, Wachner S, Gyoergy A, Emtenani S, Gridchyn I, Akhmanova M, et al, Fos regulates macrophage infiltration against surrounding tissue resistance by an actin-dependent cortical mechanism in Drosophila. Plus Biology (2022). DOI: 10.1371 / journal.pbio.3001494

Provided by Institute of Science and Technology Austria

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