Mechanism that helps immune cells to invade tissues

Date:
January 6, 2022
Source:
Institute of Science and Technology Austria
Summary:
To fight infections and heal injuries, immune cells need to
enter tissue.

They also need to invade tumors to fight them from
within. Scientists have now discovered how immune cells protect
their sensitive insides as they squeeze between tissue cells. The
team lays the foundation for identifying new targets in cancer
treatment.



FULL STORY ==========================================================================
To fight infections and heal injuries, immune cells need to
enter tissue. They also need to invade tumors to fight them from
within. Scientists have now discovered how immune cells protect their
sensitive insides as they squeeze between tissue cells. The team lays
the foundation for identifying new targets in cancer treatment.


========================================================================== Knowing, when exactly immune cells will try to invade a tumor is
difficult. In order to be able to study this cell invasion process
in detail, scientists like Professor Daria Siekhaus and her team need
something more reliable. That's why they turn to fruit fly embryos. During
the development of these embryos, macrophages, the dominant form of
immune cells in the fruit fly, travel from the spot where they are
born to the place where they are needed by invading tissue. They do
so at a certain time point, enabling scientists to study the process
within these tiny transparent animals. With the help of IST Austria's state-of-the-art Bioimaging Facility, they watch as the macrophages --
marked with a green fluorescent protein -- push their way into the tissue.

Creating an armor Which cellular changes are needed for this and which
genes trigger such alterations is still largely unknown. With their
new study by first authors Vera Belyaeva, Stephanie Wachner, and Attila Gyoergy, the Siekhaus group sheds light on this process, essential in
health and disease. "Previously, we found that a specific gene, called
Dfos, is enriched in the immune cells and we wondered what it did,"
says Siekhaus.

"Now we can prove that it triggers the assembly of actin filaments." These protein threads are concentrated at the inside of the cell membrane,
also known as cell cortex, giving the cell surface stability. The
scientists show that through a complex cascade involving different
proteins, the actin filaments are made denser and more connected to each
other, forming a stable shell. "We hypothesize that this works like a
tank, deforming surrounding cells while protecting the immune cell's
nucleus from mechanical pressure as it invades the tissue," Siekhaus
explains. Furthermore, the team was able to show in vivo that missing
this actin shell makes it harder for immune cells to infiltrate unless
the surrounding tissue is made softer.

Strengthening immune cells to fight cancer Although a fruit fly
and vertebrates such as mice and humans do not have much in common
at first glance, there are many similarities in the way their genes
function. Working together with Professor Maria Sibilia from the Medical University of Vienna, the researchers at IST Austria found evidence
that the vertebrate gene Fos, the equivalent to the fruit fly gene Dfos, activates the same genetic pathways. "We think that the same mechanism we
found in the fruit fly also plays a role in vertebrates," says biologist
Daria Siekhaus.

This raises the hope that the group's findings could help identify new
targets for the treatment of cancer. In the field of immuno-oncology, researchers are looking for ways to activate the body's immune system to
attack a tumor. One of the challenges they face, is to enable the immune
cells to infiltrate the tumor. "If one could strengthen their protective
shell, it could make it easier for them to invade the tumor tissue,"
Siekhaus concludes.

========================================================================== Story Source: Materials provided by Institute_of_Science_and_Technology_Austria. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Vera Belyaeva, Stephanie Wachner, Attila Gyoergy, Shamsi Emtenani,
Igor
Gridchyn, Maria Akhmanova, Markus Linder, Marko Roblek, Maria
Sibilia, Daria Siekhaus. Fos regulates macrophage infiltration
against surrounding tissue resistance by a cortical actin-based
mechanism in Drosophila. PLOS Biology, 2022; 20 (1): e3001494 DOI:
10.1371/journal.pbio.3001494 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220106143719.htm

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